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Sample records for animal toxicity study

  1. Toxicity studies of drugs and chemicals in animals: An overview

    Directory of Open Access Journals (Sweden)

    S. Saganuwan

    2017-12-01

    Full Text Available Toxicity study is the investigation of either short or long-term toxic effects of a drug or chemical on animals. The toxicity is dose-dependent as asserted by Paracelsus over 500 years ago. However, short-term toxic effect is determined using median lethal dose (LD50 first introduced by Trevan in 1927 and revised many times. Presently there is a growing preponderance of rejection of scientific papers on acute toxicity study, simply because of the belief that in the current hazard and safety as-sessment of drugs and chemicals, LD50 values are no longer used. In view of this, literature search was carried out with a view to investigating the relevance of LD50 in development and assessment of drugs and chemicals. The findings revealed that in the past, many animals had been used for LD50 determination. OECD has reduced the number of test animals to 5–15 and presently it is further re-duced to 2–6. Acute toxicity study is being carried out in medicinal plants research and in the study of patent medicine. Although the application of LD50 has been drastically reduced, it is still applied and accepted in some parts of the world. Moreover, animals on which LD50 tests are conducted, should be allowed to die to see the end effect of the test drug or chemical because euthanisia of test animals may mask some toxicity signs of the test agents. Therefore, toxicity study of drugs and chemicals is a sci-entific process necessary for discovery and development of drugs as well as identification of potential toxicants.

  2. Toxicity studies of drugs and chemicals in animals: An overview

    OpenAIRE

    S. Saganuwan

    2017-01-01

    Toxicity study is the investigation of either short or long-term toxic effects of a drug or chemical on animals. The toxicity is dose-dependent as asserted by Paracelsus over 500 years ago. However, short-term toxic effect is determined using median lethal dose (LD50) first introduced by Trevan in 1927 and revised many times. Presently there is a growing preponderance of rejection of scientific papers on acute toxicity study, simply because of the belief that in the current hazard and safety ...

  3. Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

    Science.gov (United States)

    Golub, M S; Macintosh, M S; Baumrind, N

    1998-01-01

    Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient.

  4. Toxic Effects of Cannabis and Cannabinoids: Animal Data

    Directory of Open Access Journals (Sweden)

    Pierre Beaulieu

    2005-01-01

    Full Text Available The present article reviews the main toxic effects of cannabis and cannabinoids in animals. Toxic effects can be separated into acute and chronic classifications. Acute toxicity studies show that it is virtually impossible to die from acute administration of marijuana or tetrahydrocannabinol, the main psychoactive component of cannabis. Chronic toxicity involves lesions of airway and lung tissues, as well as problems of neurotoxicity, tolerance and dependence, and dysregulations in the immune and hormonal systems. Animal toxicity data, however, are difficult to extrapolate to humans.

  5. [Tricholoma equestre--animal toxicity study].

    Science.gov (United States)

    Chodorowski, Zygmunt; Sznitowska, Małgorzata; Wiśniewski, Marek; Sein Anand, Jacek; Waldman, Wojciech; Ronikier, Anna

    2004-01-01

    Animal toxicity study of Tricholoma equestre mushrooms stored for 12 months at (-)20 degrees C was performed using 30 male BALB/c mice. Three groups of 5 mice each were given suspension of T. equestre powder in water, boiled aqueous extract and chloroform-methanol extract dissolved in Miglyol 812 by gavage for three consecutive days. Mice in control groups were given water, Miglyol 812 and p-phenylenediamine (CAS 106-50-3). Creatine kinase activity was determined in serum collected 72 hours after the final dose. Mean activity of serum creatine kinase in mice treated with T. equestre powder, aqueous extract, chloroform-methanol extract and Miglyol 812 were 157 +/- 93, 129 +/- 30, 96 +/- 38, 111 +/- 66 U/L respectively and did not differ significantly from mean activity in mice which were given water (107 +/- 38 U/L). Mean serum creatine kinase activity in p-phenylenediamine group (265 +/- 63 U/L) was significantly higher than in group treated with water (p<0.01). Extracts of Tricholoma equestre mushrooms stored for 12 months at (-)20 degrees C did not cause rhabdomyolysis in male BALB/c mice.

  6. STUDY OF THE TOXIC EFFECTS OF CYPERMETHRIN IN EXPERIMENTAL ANIMALS

    Directory of Open Access Journals (Sweden)

    Syed Mehmood Hasan

    2016-06-01

    Full Text Available This study focuses on the toxic effects of a commercially available pesticide, cypermethrin (CM, on animals. This pesticide was administered in the form of aerosol spray through a nebulizer. The study was performed in four different groups and a constant dose of the pesticide was administered once, twice, thrice and four times a day to the respective group for a period of 30 days. The animals were then dissected to study the pesticide effects on different organs. The organs were preserved in 10% formalin. The tissues were processed by basic histopathological method and the slides were prepared for observation. The results were recorded on a performa and were quantified by a unique scoring system. It is concluded that the injurious effects to the mentioned organs were dose and frequency dependent.

  7. Non-animal Replacements for Acute Toxicity Testing.

    Science.gov (United States)

    Barker-Treasure, Carol; Coll, Kevin; Belot, Nathalie; Longmore, Chris; Bygrave, Karl; Avey, Suzanne; Clothier, Richard

    2015-07-01

    Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients. 2015 FRAME.

  8. Two new animal models for actinide toxicity studies

    International Nuclear Information System (INIS)

    Taylor, G.N.; Gardner, P.A.; Jones, C.W.; Lloyd, R.D.; Mays, C.W.

    1979-01-01

    Two small rodent species, the grasshopper mouse (Onychomys leucogaster) and the deer mouse (Peromyscus maniculatus) have tenacious retention in the liver and skeleton of plutonium and americium. The retention following intraperitoneal injection of Pu and Am in citrate solution ranged from 20 to 47% (liver) and 19 to 42% (skeleton), relatively independent of post-injection times, varying from 30 to 125 days. Based on observations extended to 125 days post-injection, the biological half-times appeared to be long. Both of these rodents are relatively long-lived (median lifespans of approximately 1400 days), breed well in captivity, and adapt suitably to laboratory conditions. It is suggested that these two species of mice, in which plutonium is partitioned between the skeleton and liver in a manner similar to that of man, may be useful animal models for actinide toxicity studies

  9. Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

    Science.gov (United States)

    Nam, I. F.; Zhuk, V. V.

    2015-04-01

    Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

  10. Role of animal toxicity studies in the evaluation of human health risks from internally deposited transuranics

    International Nuclear Information System (INIS)

    Thompson, R.C.

    1977-02-01

    The extrapolation of animal data to man has always been a problem for those concerned with human biology. Especially if one is interested in the effects of toxicants, opportunities for direct observation in man are usually limited, and approval of planned experiments employing human subjects is difficult to obtain. In no case are these limitations more restrictive than for transuranic elements, for which no life-threatening effects have yet been demonstrated in man. This lack of human experience is coupled with a massive public concern over possible future effects of transuranics, which contrasts sharply with the general public apathy toward a multitude of present environmental pollutants of clearly established toxicity. This concern for the transuranics, especially 239 Pu, and for other radionuclides has prompted the expenditure of many millions of dollars (and francs and marks and pounds and roubles) on studies to investigate their toxicity in animals. Results of these studies are extensive, and still accumulating, but in many quarters there is now a reluctance to accept these results as relevant to the prediction of human effects

  11. Molecular Mechanisms of Microcystin Toxicity in Animal Cells

    Directory of Open Access Journals (Sweden)

    Alexandre Campos

    2010-01-01

    Full Text Available Microcystins (MC are potent hepatotoxins produced by the cyanobacteria of the genera Planktothrix, Microcystis, Aphanizomenon, Nostoc and Anabaena. These cyclic heptapeptides have strong affinity to serine/threonine protein phosphatases (PPs thereby acting as an inhibitor of this group of enzymes. Through this interaction a cascade of events responsible for the MC cytotoxic and genotoxic effects in animal cells may take place. Moreover MC induces oxidative stress in animal cells and together with the inhibition of PPs, this pathway is considered to be one of the main mechanisms of MC toxicity. In recent years new insights on the key enzymes involved in the signal-transduction and toxicity have been reported demonstrating the complexity of the interaction of these toxins with animal cells. Key proteins involved in MC up-take, biotransformation and excretion have been identified, demonstrating the ability of aquatic animals to metabolize and excrete the toxin. MC have shown to interact with the mitochondria. The consequences are the dysfunction of the organelle, induction of reactive oxygen species (ROS and cell apoptosis. MC activity leads to the differential expression/activity of transcriptional factors and protein kinases involved in the pathways of cellular differentiation, proliferation and tumor promotion activity. This activity may result from the direct inhibition of the protein phosphatases PP1 and PP2A. This review aims to summarize the increasing data regarding the molecular mechanisms of MC toxicity in animal systems, reporting for direct MC interacting proteins and key enzymes in the process of toxicity biotransformation/excretion of these cyclic peptides.

  12. Animal data on plutonium toxicity

    International Nuclear Information System (INIS)

    Thompson, R.C.

    1975-01-01

    Animal data are necessary in the assessment of plutonium toxicity since it is unlikely that the necessary information on effects from humans will be obtained. Experiments on animals must be designed to provide understanding of the mechanisms at work if the results are to be applied to man since it is a statistical impossibility to design experiments to measure directly the low levels of risk that are of concern. Cancer induction appears to be the risk of greatest concern with the lung and bone apparently the most susceptible organs, depending upon the method of administration. Current limitations on these organs do not appear to have the safety margin formerly believed and there are some uncertainties in the extrapolation from animal data to man. (author)

  13. Animal alternatives for whole effluent toxicity testing ...

    Science.gov (United States)

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicity based effluent assessments and subsequent discharge controls became globally important, when it was recognized that physical and chemical measurements alone did not protect the environment from potential impacts. Consequently, various strategies using different toxicity tests, whole effluent assessment techniques (incorporating bioaccumulation potential and persistence) plus supporting analytical tools have been developed over 30 years of practice. Numerous workshops and meetings have focused on effluent risk assessment through ASTM, SETAC, OSPAR, UK competent authorities, and EU specific country rules. Concurrent with this drive to improve effluent quality using toxicity tests, interest in reducing animal use has risen. The Health and Environmental Sciences Institute (HESI) organized and facilitated an international workshop in March 2016 to evaluate strategies for concepts, tools, and effluent assessments and update the toolbox of for effluent testing methods. The workshop objectives were to identify opportunities to use a suite of strategies for effluents, and to identify opportunities to reduce the reliance on animal tests and to determine barriers to implementation of new methodologie

  14. Is Boric Acid Toxic to Reproduction in Humans? Assessment of the Animal Reproductive Toxicity Data and Epidemiological Study Results.

    Science.gov (United States)

    Duydu, Yalçın; Başaran, Nurşen; Ustündağ, Aylin; Aydın, Sevtap; Undeğer, Ulkü; Ataman, Osman Yavuz; Aydos, Kaan; Düker, Yalçın; Ickstadt, Katja; Waltrup, Brita Schulze; Golka, Klaus; Bolt, Hermann Maximilian

    2016-01-01

    Boric acid and sodium borates are classified as toxic to reproduction in the CLP Regulation under "Category 1B" with the hazard statement of "H360FD". This classification is based on the reprotoxic effects of boric acid and sodium borates in animal experiments at high doses. However, boron mediated reprotoxic effects have not been proven in epidemiological studies so far. The epidemiological study performed in Bandırma boric acid production plant is the most comprehensive published study in this field with 204 voluntarily participated male workers. Sperm quality parameters (sperm morphology, concentration and motility parameters), FSH, LH and testosterone levels were determined in all participated employees as the reproductive toxicity biomarkers of males. However, boron mediated unfavorable effects on reproduction in male workers have not been determined even in the workers under very high daily boron exposure (0.21 mg B/kg-bw/day) conditions. The NOAEL for rat reproductive toxicity is equivalent to a blood boron level of 2020 ng/g. This level is higher than the mean blood boron concentration (223.89 ± 69.49 ng/g) of the high exposure group workers in Bandırma boric acid production plant (Turkey) by a factor of 9. Accordingly, classifying boric acid and sodium borates under "Category 1B" as "presumed reproductive human toxicant in the CLP regulation seems scientifically not reasonable. The results of the epidemiological studies (including the study performed in China) support for a down-classification of boric acid from the category 1B, H360FD to category 2, H361d, (suspected of damaging the unborn child).

  15. The results of the toxicity and hazard studies of isopropyl meta-carborane with single administration to laboratory animals

    Directory of Open Access Journals (Sweden)

    Yushkov G.G.

    2018-04-01

    Full Text Available Intensive research on the chemistry of borohydrides and the creation of high-energy fuels led to the discovery of a completely new type of organoboron compounds, which were collectively called carboranes. Taking into account the scope of application of organoboron compounds in various branches of human economic activity, we present for publication the quantitative data of a toxicological study of the higher isomer of carboranes of isopropyl meta-carborane at the level of a single injection into the laboratory animals through the mouth and lungs. Background. Supplementing data on toxicity and the hazard of organoboron compounds requires the study of the response of the organism to the action of isopropyl meta-carborane. The purpose of the study: identification of possible features and specificity of the toxic effect of carboranes on the example of isopropyl meta-carborane. Methods. The object of the study is nonlinear laboratory animals: rats, mice and rabbits contained in standard vivarium conditions, with observance of the rules of humane treatment of animals. Traditional methods of research (physiological, hematological, morphological have been used. Statistical processing of data was carried out using the programs «Microsoft Office Excel 2007» and «Biostat». Differences were considered statistically significant at p ≤ 0.05, using a parametric test. Results. Acute toxicity parameters were obtained, which allowed the substance to be classified as moderately hazardous (3rd hazard class according to GOST 12.1.007, which does not have selective irritant, pneumotoxic and fibrogenic effects. Conclusion. Thus, the predominant influence of the substance is established objectively with a single exposure to the blood system as its toxicological feature, and its effect on spermatozoa is a specificity of the action, which stimulates the study of this carborane under conditions of chronic administration to the animals.

  16. Isotope techniques in studies of selenium deficiency and toxicity syndromes in farm animals

    International Nuclear Information System (INIS)

    Giese, W.W.

    1984-01-01

    In a brief review of the Se deficiency syndrome in ruminants, studies using non-isotopic methods are applied to an introductory description of the disease. They include methods currently applied for determining Se deficiency status in feed and in ruminant animals. Detection of potential white muscle disease in lambs and calves is discussed. The application of 75 Se in studies on absorption, tissue distribution and excretion under feeding regimes with different Se levels and partly with addition of SO 4 ions or vitamin E is reviewed. In vitro studies with 75 Se include a description of the 75 Se uptake test with red blood cells, the metabolism of selenite, selenate and selenomethionine in rumen microorganisms, and the distribution of 75 Se in cow's and goat's milk. Methods of Se supplementation in Se-deficient areas are summarized and tests with 75 Se-labelled ruminal pellets in sheep and cattle are described. The Se toxicity syndrome is surveyed with respect to causative agents, symptomatology and gross pathology. Special reference is made to the blind staggers and the alkali disease types of selenosis. Isotope techniques are found to be less frequently applied in studies on Se toxicity than in Se deficiency studies. (author)

  17. Review of pulmonary toxicity of indium compounds to animals and humans

    International Nuclear Information System (INIS)

    Tanaka, Akiyo; Hirata, Miyuki; Kiyohara, Yutaka; Nakano, Makiko; Omae, Kazuyuki; Shiratani, Masaharu; Koga, Kazunori

    2010-01-01

    Due to the increased production of ITO, the potential health hazards arising from occupational exposure to this material have attracted much attention. This review consists of three parts: 1) toxic effects of indium compounds on animals, 2) toxic effects of indium compounds on humans, and 3) recommendations for preventing exposure to indium compounds in the workplace. Available data have indicated that insoluble form of indium compounds, such as ITO, indium arsenide (InAs) and indium phosphide (InP), can be toxic to animals. Furthermore, InP has demonstrated clear evidence of carcinogenic potential in long-term inhalation studies using experimental animals. As for the dangers to humans, some data are available concerning adverse health effects to workers who have been exposed to indium-containing particles. The Japan Society for Occupational Health recommended the value of 3 μg/L of indium in serum as the occupational exposure limit based on biological monitoring to preventing adverse health effects in workers resulting from occupational exposure to indium compounds. Accordingly, it is essential that much greater attention is focused on human exposure to indium compounds, and precautions against possible exposure to indium compounds are most important with regard to health management among indium-handling workers.

  18. A method for comparison of animal and human alveolar dose and toxic effect of inhaled ozone

    International Nuclear Information System (INIS)

    Hatch, G.E.; Koren, H.; Aissa, M.

    1989-01-01

    Present models for predicting the pulmonary toxicity of O 3 in humans from the toxic effects observed in animals rely on dosimetric measurements of O 3 mass balance and species comparisons of mechanisms that protect tissue against O 3 . The goal of the study described was to identify a method to directly compare O 3 dose and effect in animals and humans using bronchoalveolar lavage fluid markers. The feasibility of estimating O 3 dose to alveoli of animals and humans was demonstrated through assay of reaction products of 18 O-labeled O 3 in lung surfactant and macrophage pellets of rabbits. The feasibility of using lung lavage fluid protein measurements to quantify the O 3 toxic response in humans was demonstrated by the finding of significantly increased lung lavage protein in 10 subjects exposed to 0.4 ppm O 3 for 2 h with intermittent periods of heavy exercise. The validity of using the lavage protein marker to quantify the response in animals has already been established. The positive results obtained in both the 18 O 3 and the lavage protein studies reported here suggest that it should be possible to obtain a direct comparison of both alveolar dose and toxic effect of O 3 to alveoli of animals or humans

  19. Non-animal methodologies within biomedical research and toxicity testing.

    Science.gov (United States)

    Knight, Andrew

    2008-01-01

    Laboratory animal models are limited by scientific constraints on human applicability, and increasing regulatory restrictions, driven by social concerns. Reliance on laboratory animals also incurs marked - and in some cases, prohibitive - logistical challenges, within high-throughput chemical testing programmes, such as those currently underway within Europe and the US. However, a range of non-animal methodologies is available within biomedical research and toxicity testing. These include: mechanisms to enhance the sharing and assessment of existing data prior to conducting further studies, and physicochemical evaluation and computerised modelling, including the use of structure-activity relationships and expert systems. Minimally-sentient animals from lower phylogenetic orders or early developmental vertebral stages may be used, as well as microorganisms and higher plants. A variety of tissue cultures, including immortalised cell lines, embryonic and adult stem cells, and organotypic cultures, are also available. In vitro assays utilising bacterial, yeast, protozoal, mammalian or human cell cultures exist for a wide range of toxic and other endpoints. These may be static or perfused, and may be used individually, or combined within test batteries. Human hepatocyte cultures and metabolic activation systems offer potential assessment of metabolite activity and organ-organ interaction. Microarray technology may allow genetic expression profiling, increasing the speed of toxin detection, well prior to more invasive endpoints. Enhanced human clinical trials utilising micro- dosing, staggered dosing, and more representative study populations and durations, as well as surrogate human tissues, advanced imaging modalities and human epidemiological, sociological and psycho- logical studies, may increase our understanding of illness aetiology and pathogenesis, and facilitate the development of safe and effective pharmacologic interventions. Particularly when human tissues

  20. Toxicity testing: the search for an in vitro alternative to animal testing.

    Science.gov (United States)

    May, J E; Xu, J; Morse, H R; Avent, N D; Donaldson, C

    2009-01-01

    Prior to introduction to the clinic, pharmaceuticals must undergo rigorous toxicity testing to ensure their safety. Traditionally, this has been achieved using in vivo animal models. However, besides ethical reasons, there is a continual drive to reduce the number of animals used for this purpose due to concerns such as the lack of concordance seen between animal models and toxic effects in humans. Adequate testing to ensure any toxic metabolites are detected can be further complicated if the agent is administered in a prodrug form, requiring a source of cytochrome P450 enzymes for metabolism. A number of sources of metabolic enzymes have been utilised in in vitro models, including cell lines, primary human tissue and liver extracts such as S9. This review examines current and new in vitro models for toxicity testing, including a new model developed within the authors' laboratory utilising HepG2 liver spheroids within a co-culture system to examine the effects of chemotherapeutic agents on other cell types.

  1. Animal Testing for Acute Inhalation Toxicity: A Thing of the Past?

    DEFF Research Database (Denmark)

    Da Silva, Emilie; Sørli, Jorid Birkelund

    2018-01-01

    According to REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals), testing for acute inhalation toxicity is required for chemicals manufactured or imported at tonnages ≥ 10 tons per year. Three OECD test guidelines for acute inhalation toxicity in vivo are adopted (TG 403......, TG 436, and TG 433). Since animal testing is ethically, scientifically and economically questionable, adoption of alternative methods by the European Union and the OECD is needed. An in vitro system based on the study of lung surfactant function is introduced....

  2. Study of the relative toxicity of anions, with Polycelis nigra as test animal

    Energy Technology Data Exchange (ETDEWEB)

    Jones, J R.E.

    1942-01-01

    A brief review is given of existing knowledge regarding the physiological effects of anions, and literature dealing with their relative toxicity. The degree of toxicity of twenty-seven anions to Polycelis nigra (Mueller) has been assessed, by determining in each case the molar concentration the animal survives for 48 hr. at 15-18/sup 0/C. On this basis their order of increasing toxicity is as follows; commas separate ions of similar degree of toxicity: Cltoxic than cations. Even the most toxic anion (OH) is far less toxic than ionic copper, silver, or gold. The respiration rate of Polycelis is heavily depressed by cyanide, but the survival time is three days or longer, as long as the respiration rate is not less than about 16% of the normal value. With further depression the survival time shortens rapidly, and at 9% normal is under 4 hr. The normal respiration rate of Polycelis nigra is 0.165 cc O/sub 2//g./hr. This is not very much less than that of the trout. Polycelis is considerably the more resistant to cyanide. This is probably connected with its capability of surviving very many hours in water containing a very reduced supply of oxygen. 34 references, 6 figures, 1 table.

  3. Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review.

    Science.gov (United States)

    Brohi, Rahim Dad; Wang, Li; Talpur, Hira Sajjad; Wu, Di; Khan, Farhan Anwar; Bhattarai, Dinesh; Rehman, Zia-Ur; Farmanullah, F; Huo, Li-Jun

    2017-01-01

    In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations.

  4. ACUTE TOXICITY STUDIES AND ANTIDOTAL THERAPY OF ...

    African Journals Online (AJOL)

    ACUTE TOXICITY STUDIES AND ANTIDOTAL THERAPY OF ETHANOL EXTRACT OF JATROPHA CURCAS SEEDS IN EXPERIMENTAL ANIMALS. ... with the aim of investigating the toxicity of the ethanol seed extract of JC in rats, mice, and chicks; and also to use conventional antidotes to treat intoxication in rats due to ...

  5. Consensus report on the future of animal-free systemic toxicity testing.

    Science.gov (United States)

    Leist, Marcel; Hasiwa, Nina; Rovida, Costanza; Daneshian, Mardas; Basketter, David; Kimber, Ian; Clewell, Harvey; Gocht, Tilman; Goldberg, Alan; Busquet, Francois; Rossi, Anna-Maria; Schwarz, Michael; Stephens, Martin; Taalman, Rob; Knudsen, Thomas B; McKim, James; Harris, Georgina; Pamies, David; Hartung, Thomas

    2014-01-01

    Since March 2013, animal use for cosmetics testing for the European market has been banned. This requires a renewed view on risk assessment in this field. However, in other fields as well, traditional animal experimentation does not always satisfy requirements in safety testing, as the need for human-relevant information is ever increasing. A general strategy for animal-free test approaches was outlined by the US National Research Council`s vision document for Toxicity Testing in the 21st Century in 2007. It is now possible to provide a more defined roadmap on how to implement this vision for the four principal areas of systemic toxicity evaluation: repeat dose organ toxicity, carcinogenicity, reproductive toxicity and allergy induction (skin sensitization), as well as for the evaluation of toxicant metabolism (toxicokinetics) (Fig. 1). CAAT-Europe assembled experts from Europe, America and Asia to design a scientific roadmap for future risk assessment approaches and the outcome was then further discussed and refined in two consensus meetings with over 200 stakeholders. The key recommendations include: focusing on improving existing methods rather than favoring de novo design; combining hazard testing with toxicokinetics predictions; developing integrated test strategies; incorporating new high content endpoints to classical assays; evolving test validation procedures; promoting collaboration and data-sharing of different industrial sectors; integrating new disciplines, such as systems biology and high throughput screening; and involving regulators early on in the test development process. A focus on data quality, combined with increased attention to the scientific background of a test method, will be important drivers. Information from each test system should be mapped along adverse outcome pathways. Finally, quantitative information on all factors and key events will be fed into systems biology models that allow a probabilistic risk assessment with flexible

  6. Consensus report on the future of animal-free systemic toxicity testing

    OpenAIRE

    Leist, Marcel; Hasiwa, Nina; Rovida, Costanza; Daneshian, Mardas; Basketter, David; Kimber, Ian; Clewell, Harvey; Gocht, Tilman; Goldberg, Alan; Busquet, Francois; Rossi, Anna-Maria; Schwarz, Michael; Stephens, Martin; Taalman, Rob; Knudsen, Thomas B

    2014-01-01

    Since March 2013, animal use for cosmetics testing for the European market has been banned. This requires a renewed view on risk assessment in this field. However, in other fields as well, traditional animal experimentation does not always satisfy requirements in safety testing, as the need for human-relevant information is ever increasing. A general strategy for animal-free test approaches was outlined by the US National Research Council`s vision document for Toxicity Testing in the 21st Cen...

  7. Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review

    Science.gov (United States)

    Brohi, Rahim Dad; Wang, Li; Talpur, Hira Sajjad; Wu, Di; Khan, Farhan Anwar; Bhattarai, Dinesh; Rehman, Zia-Ur; Farmanullah, F.; Huo, Li-Jun

    2017-01-01

    In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations. PMID:28928662

  8. Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review

    Directory of Open Access Journals (Sweden)

    Rahim Dad Brohi

    2017-09-01

    Full Text Available In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations.

  9. Assessment of diurnal systemic dose of agrochemicals in regulatory toxicity testing--an integrated approach without additional animal use.

    Science.gov (United States)

    Saghir, Shakil A; Bartels, Michael J; Rick, David L; McCoy, Alene T; Rasoulpour, Reza J; Ellis-Hutchings, Robert G; Sue Marty, M; Terry, Claire; Bailey, Jason P; Billington, Richard; Bus, James S

    2012-07-01

    Integrated toxicokinetics (TK) data provide information on the rate, extent and duration of systemic exposure across doses, species, strains, gender, and life stages within a toxicology program. While routine for pharmaceuticals, TK assessments of non-pharmaceuticals are still relatively rare, and have never before been included in a full range of guideline studies for a new agrochemical. In order to better understand the relationship between diurnal systemic dose (AUC(24h)) and toxicity of agrochemicals, TK analyses in the study animals is now included in all short- (excluding acute), medium- and long-term guideline mammalian toxicity studies including reproduction/developmental tests. This paper describes a detailed procedure for the implementation of TK in short-, medium- and long-term regulatory toxicity studies, without the use of satellite animals, conducted on three agrochemicals (X11422208, 2,4-D and X574175). In these studies, kinetically-derived maximum doses (KMD) from short-term studies instead of, or along with, maximum tolerated doses (MTD) were used for the selection of the high dose in subsequent longer-term studies. In addition to leveraging TK data to guide dose level selection, the integrated program was also used to select the most appropriate method of oral administration (i.e., gavage versus dietary) of test materials for rat and rabbit developmental toxicity studies. The integrated TK data obtained across toxicity studies (without the use of additional/satellite animals) provided data critical to understanding differences in response across doses, species, strains, sexes, and life stages. Such data should also be useful in mode of action studies and to improve human risk assessments. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Animal models of disease: feline hyperthyroidism: an animal model for toxic nodular goiter.

    Science.gov (United States)

    Peterson, Mark E

    2014-11-01

    Since first discovered just 35 years ago, the incidence of spontaneous feline hyperthyroidism has increased dramatically to the extent that it is now one of the most common disorders seen in middle-aged to senior domestic cats. Hyperthyroid cat goiters contain single or multiple autonomously (i.e. TSH-independent) functioning and growing thyroid nodules. Thus, hyperthyroidism in cats is clinically and histologically similar to toxic nodular goiter in humans. The disease in cats is mechanistically different from Graves' disease, because neither the hyperfunction nor growth of these nodules depends on extrathyroidal circulating stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells, but iodine deficiency, other nutritional goitrogens, or environmental disruptors may play a role in the disease pathogenesis. Clinical features of feline toxic nodular goiter include one or more palpable thyroid nodules, together with signs of hyperthyroidism (e.g. weight loss despite an increased appetite). Diagnosis of feline hyperthyroidism is confirmed by finding the increased serum concentrations of thyroxine and triiodothyronine, undetectable serum TSH concentrations, or increased thyroid uptake of radioiodine. Thyroid scintigraphy demonstrates a heterogeneous pattern of increased radionuclide uptake, most commonly into both thyroid lobes. Treatment options for toxic nodular goiter in cats are similar to that used in humans and include surgical thyroidectomy, radioiodine, and antithyroid drugs. Most authorities agree that ablative therapy with radioiodine is the treatment of choice for most cats with toxic nodular goiter, because the animals are older, and the disease will never go into remission. © 2014 Society for Endocrinology.

  11. Animal toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Amdur, M.

    1996-12-31

    The chapter evaluates results of toxicological studies on experimental animals to investigate health effects of air pollutants and examines the animal data have predicted the response to human subject. Data are presented on the comparative toxicity of sulfur dioxide and sulfuric acid. The animal data obtained by measurement of airway resistance in guinea pigs and of bronchial clearance of particles in donkeys predicted clearly that sulfuric acid was more irritant than sulfur dioxide. Data obtained on human subjects confirmed this prediction. These acute studies also correctly predicted the comparative toxicity of the two compounds in two year studies of monkeys. Such chronic studies are not possible in human subjects but it is a reasonable to assume that sulfuric acid would be more toxic than sulfur dioxide. Current findings in epidemiological studies certainly support this assumption.

  12. A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report*.

    Science.gov (United States)

    Basketter, David A; Clewell, Harvey; Kimber, Ian; Rossi, Annamaria; Blaauboer, Bas; Burrier, Robert; Daneshian, Mardas; Eskes, Chantra; Goldberg, Alan; Hasiwa, Nina; Hoffmann, Sebastian; Jaworska, Joanna; Knudsen, Thomas B; Landsiedel, Robert; Leist, Marcel; Locke, Paul; Maxwell, Gavin; McKim, James; McVey, Emily A; Ouédraogo, Gladys; Patlewicz, Grace; Pelkonen, Olavi; Roggen, Erwin; Rovida, Costanza; Ruhdel, Irmela; Schwarz, Michael; Schepky, Andreas; Schoeters, Greet; Skinner, Nigel; Trentz, Kerstin; Turner, Marian; Vanparys, Philippe; Yager, James; Zurlo, Joanne; Hartung, Thomas

    2012-01-01

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds especially true in the context of the scheduled 2013 marketing ban on cosmetic ingredients tested for systemic toxicity. Based on a major analysis of the status of alternative methods (Adler et al., 2011) and its independent review (Hartung et al., 2011), the present report proposes a roadmap for how to overcome the acknowledged scientific gaps for the full replacement of systemic toxicity testing using animals. Five whitepapers were commissioned addressing toxicokinetics, skin sensitization, repeated-dose toxicity, carcinogenicity, and reproductive toxicity testing. An expert workshop of 35 participants from Europe and the US discussed and refined these whitepapers, which were subsequently compiled to form the present report. By prioritizing the many options to move the field forward, the expert group hopes to advance regulatory science.

  13. Benzodiazepines and antipsychotic medications for treatment of acute cocaine toxicity in animal models--a systematic review and meta-analysis.

    Science.gov (United States)

    Heard, Kennon; Cleveland, Nathan R; Krier, Shay

    2011-11-01

    There are no controlled human studies to determine the efficacy of benzodiazepines or antipsychotic medications for prevention or treatment of acute cocaine toxicity. The only available controlled data are from animal models and these studies have reported inconsistent benefits. The objective of this study was to quantify the reported efficacy of benzodiazepines and antipsychotic medication for the prevention of mortality due to cocaine poisoning. We conducted a systematic review to identify English language articles describing experiments that compared a benzodiazepine or antipsychotic medication to placebo for the prevention of acute cocaine toxicity in an animal model. We then used these articles in a meta-analysis with a random-effects model to quantify the absolute risk reduction observed in these experiments. We found 10 articles evaluating antipsychotic medications and 15 articles evaluating benzodiazepines. Antipsychotic medications reduced the risk of death by 27% (95% CI, 15.2%-38.7%) compared to placebo and benzodiazepines reduced the risk of death by 52% (42.8%-60.7%) compared to placebo. Both treatments showed evidence of a dose-response effect, and no experiment found a statistically significant increase in risk of death. We conclude that both benzodiazepines and antipsychotic medications are effective for the prevention of lethality from cocaine toxicity in animal models.

  14. Bias During the Evaluation of Animal Studies?

    Directory of Open Access Journals (Sweden)

    Andrew Knight

    2012-02-01

    Full Text Available My recent book entitled The Costs and Benefits of Animal Experiments seeks to answer a key question within animal ethics, namely: is animal experimentation ethically justifiable? Or, more precisely, is it justifiable within the utilitarian cost:benefit framework that fundamentally underpins most regulations governing animal experimentation? To answer this question I reviewed more than 500 scientific publications describing animal studies, animal welfare impacts, and alternative research, toxicity testing and educational methodologies. To minimise bias I focused primarily on large-scale systematic reviews that had examined the human clinical and toxicological utility of animal studies. Despite this, Dr. Susanne Prankel recently reviewed my book in this journal, essentially accusing me of bias. However, she failed to provide any substantive evidence to refute my conclusions, let alone evidence of similar weight to that on which they are based. Those conclusions are, in fact, firmly based on utilitarian ethical reasoning, informed by scientific evidence of considerable strength, and I believe they are robust.

  15. Bias During the Evaluation of Animal Studies?

    Science.gov (United States)

    Knight, Andrew

    2012-02-23

    My recent book entitled The Costs and Benefits of Animal Experiments seeks to answer a key question within animal ethics, namely: is animal experimentation ethically justifiable? Or, more precisely, is it justifiable within the utilitarian cost:benefit framework that fundamentally underpins most regulations governing animal experimentation? To answer this question I reviewed more than 500 scientific publications describing animal studies, animal welfare impacts, and alternative research, toxicity testing and educational methodologies. To minimise bias I focused primarily on large-scale systematic reviews that had examined the human clinical and toxicological utility of animal studies. Despite this, Dr. Susanne Prankel recently reviewed my book in this journal, essentially accusing me of bias. However, she failed to provide any substantive evidence to refute my conclusions, let alone evidence of similar weight to that on which they are based. Those conclusions are, in fact, firmly based on utilitarian ethical reasoning, informed by scientific evidence of considerable strength, and I believe they are robust.

  16. Body-on-a-chip systems for animal-free toxicity testing.

    Science.gov (United States)

    Mahler, Gretchen J; Esch, Mandy B; Stokol, Tracy; Hickman, James J; Shuler, Michael L

    2016-10-01

    Body-on-a-chip systems replicate the size relationships of organs, blood distribution and blood flow, in accordance with human physiology. When operated with tissues derived from human cell sources, these systems are capable of simulating human metabolism, including the conversion of a prodrug to its effective metabolite, as well as its subsequent therapeutic actions and toxic side-effects. The system also permits the measurement of human tissue electrical and mechanical reactions, which provide a measure of functional response. Since these devices can be operated with human tissue samples or with in vitro tissues derived from induced pluripotent stem cells (iPS), they can play a significant role in determining the success of new pharmaceuticals, without resorting to the use of animals. By providing a platform for testing in the context of human metabolism, as opposed to animal models, the systems have the potential to eliminate the use of animals in preclinical trials. This article will review progress made and work achieved as a direct result of the 2015 Lush Science Prize in support of animal-free testing. 2016 FRAME.

  17. Summary of safety evaluation toxicity studies of glufosinate ammonium.

    Science.gov (United States)

    Ebert, E; Leist, K H; Mayer, D

    1990-05-01

    This article reviews the results of toxicity studies to evaluate the safety of the herbicide glufosinate ammonium (GLA) and its formulation (200 g/litre) in laboratory animals. The data show that GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced slight dermal toxicity and eye irritation. Testing for teratogenicity in rats and rabbits indicated no teratogenic potential, and numerous mutagenicity tests showed GLA to be non-genotoxic. Chronic toxicity testing in rats and dogs yielded no-observable-effect levels of 2 and 5 mg/kg body weight/day, respectively. Oncogenicity studies in rats and mice revealed no carcinogenic potential. On the basis of these toxicity data it is concluded that this herbicide is safe under conditions of recommended use.

  18. Acute and subchronic toxicity studies of methanol extract of Polygonum minus leaves in Sprague Dawley rats.

    Science.gov (United States)

    Christapher, Parayil Varghese; Parasuraman, Subramani; Asmawi, Mohd Zaini; Murugaiyah, Vikneswaran

    2017-06-01

    Medicinal plant preparations may contain high levels of toxic chemical constituents to potentially cause serious harm to animals and/or humans. Thus, toxicity studies are important to assess the toxic effects of plant derived products. Polygonum minus is used traditionally for different ailments in Southeast Asia. This study was conducted to establish the acute and subchronic toxicity profile of the methanol extract of P. minus leaves. The acute toxicity study showed that the methanol extract of P. minus is safe even at the highest dose tested of 2000 mg/kg in female Sprague Dawley rats. There were no behavioural or physiological changes and gross pathological abnormalities observed. The subchronic toxicity study of methanol extract of P. minus at 250, 500, 1000 and 2000 mg/kg were conducted in both sexes of Sprague Dawley rats. There were no changes observed in the extract treated animal's body weight, food and water intake, motor coordination, behaviour and mental alertness. The values of haematological and biochemical parameters were not different between the treated and control animals. The relative organ weights of extract-treated animals did not differ with that of control animals. Based on the present findings, the methanol extract of P. minus leaves could be considered safe up to the dose of 2000 mg/kg. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Studies on the toxic interaction between monensin and tiamulin in rats: toxicity and pathology.

    Science.gov (United States)

    Szücs, G; Bajnógel, J; Varga, A; Móra, Z; Laczay, P

    2000-01-01

    The characteristics of the toxic interaction between monensin and tiamulin were investigated in rats. A three-day comparative oral repeated-dose toxicity study was performed in Phase I, when the effects of monensin and tiamulin were studied separately (monensin 10, 30, and 50 mg/kg or tiamulin 40, 120, and 200 mg/kg body weight, respectively). In Phase II, the two compounds were administered simultaneously to study the toxic interaction (monensin 10 mg/kg and tiamulin 40 mg/kg b.w., respectively). Monensin proved to be toxic to rats at doses of 30 and 50 mg/kg. Tiamulin was well tolerated up to the dose of 200 mg/kg. After combined administration, signs of toxicity were seen (including lethality in females). Monensin caused a dose-dependent cardiotoxic effect and vacuolar degeneration of the skeletal muscles in the animals given 50 mg/kg. Both compounds exerted a toxic effect on the liver in high doses. After simultaneous administration of the two compounds, there was a mild effect on the liver (females only), hydropic degeneration of the myocardium and vacuolar degeneration of the skeletal muscles. The alteration seen in the skeletal muscles was more marked than that seen after the administration of 50 mg/kg monensin alone.

  20. Testing strategies for embryo-fetal toxicity of human pharmaceuticals. Animal models vs. in vitro approaches: a workshop report.

    Science.gov (United States)

    van der Laan, Jan Willem; Chapin, Robert E; Haenen, Bert; Jacobs, Abigail C; Piersma, Aldert

    2012-06-01

    Reproductive toxicity testing is characterized by high animal use. For registration of pharmaceutical compounds, developmental toxicity studies are usually conducted in both rat and rabbits. Efforts have been underway for a long time to design alternatives to animal use. Implementation has lagged, partly because of uncertainties about the applicability domain of the alternatives. The reproductive cycle is complex and not all mechanisms of development can be mimicked in vitro. Therefore, efforts are underway to characterize the available alternative tests with regard to the mechanism of action they include. One alternative test is the mouse embryonic stem cell test (EST), which has been studied since the late 1990s. It is a genuine 3R "alternative" assay as it is essentially animal-free. A meeting was held to review the state-of-the-art of various in vitro models for prediction of developmental toxicity. Although the predictivity of individual assays is improving, a battery of several assays is likely to have even higher predictivity, which is necessary for regulatory acceptance. The workshop concluded that an important first step is a thorough survey of the existing rat and rabbit studies, to fully characterize the frequency of responses and the types of effects seen. At the same time, it is important to continue the optimization of in vitro assays. As more experience accumulates, the optimal conditions, assay structure, and applicability of the alternative assays are expected to emerge. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. The risk of contamination of food with toxic substances present in animal feed

    NARCIS (Netherlands)

    Kan, C.A.; Meijer, G.A.L.

    2007-01-01

    Toxic substances such as dioxins, mycotoxins, heavy metals, pesticides, veterinary drugs and polycyclic aromatic hydrocarbons are almost ubiquitous in the environment. Thus, they are also present in ingredients for animal feed. Adequate risk management depends on knowledge of absorption, metabolism,

  2. A multi-endpoint, high-throughput study of nanomaterial toxicity in Caenorhabditis elegans

    Science.gov (United States)

    Jung, Sang-Kyu; Qu, Xiaolei; Aleman-Meza, Boanerges; Wang, Tianxiao; Riepe, Celeste; Liu, Zheng; Li, Qilin; Zhong, Weiwei

    2015-01-01

    The booming nanotech industry has raised public concerns about the environmental health and safety impact of engineered nanomaterials (ENMs). High-throughput assays are needed to obtain toxicity data for the rapidly increasing number of ENMs. Here we present a suite of high-throughput methods to study nanotoxicity in intact animals using Caenorhabditis elegans as a model. At the population level, our system measures food consumption of thousands of animals to evaluate population fitness. At the organism level, our automated system analyzes hundreds of individual animals for body length, locomotion speed, and lifespan. To demonstrate the utility of our system, we applied this technology to test the toxicity of 20 nanomaterials under four concentrations. Only fullerene nanoparticles (nC60), fullerol, TiO2, and CeO2 showed little or no toxicity. Various degrees of toxicity were detected from different forms of carbon nanotubes, graphene, carbon black, Ag, and fumed SiO2 nanoparticles. Aminofullerene and UV irradiated nC60 also showed small but significant toxicity. We further investigated the effects of nanomaterial size, shape, surface chemistry, and exposure conditions on toxicity. Our data are publicly available at the open-access nanotoxicity database www.QuantWorm.org/nano. PMID:25611253

  3. Classification of baseline toxicants for QSAR predictions to replace fish acute toxicity studies.

    Science.gov (United States)

    Nendza, Monika; Müller, Martin; Wenzel, Andrea

    2017-03-22

    Fish acute toxicity studies are required for environmental hazard and risk assessment of chemicals by national and international legislations such as REACH, the regulations of plant protection products and biocidal products, or the GHS (globally harmonised system) for classification and labelling of chemicals. Alternative methods like QSARs (quantitative structure-activity relationships) can replace many ecotoxicity tests. However, complete substitution of in vivo animal tests by in silico methods may not be realistic. For the so-called baseline toxicants, it is possible to predict the fish acute toxicity with sufficient accuracy from log K ow and, hence, valid QSARs can replace in vivo testing. In contrast, excess toxicants and chemicals not reliably classified as baseline toxicants require further in silico, in vitro or in vivo assessments. Thus, the critical task is to discriminate between baseline and excess toxicants. For fish acute toxicity, we derived a scheme based on structural alerts and physicochemical property thresholds to classify chemicals as either baseline toxicants (=predictable by QSARs) or as potential excess toxicants (=not predictable by baseline QSARs). The step-wise approach identifies baseline toxicants (true negatives) in a precautionary way to avoid false negative predictions. Therefore, a certain fraction of false positives can be tolerated, i.e. baseline toxicants without specific effects that may be tested instead of predicted. Application of the classification scheme to a new heterogeneous dataset for diverse fish species results in 40% baseline toxicants, 24% excess toxicants and 36% compounds not classified. Thus, we can conclude that replacing about half of the fish acute toxicity tests by QSAR predictions is realistic to be achieved in the short-term. The long-term goals are classification criteria also for further groups of toxicants and to replace as many in vivo fish acute toxicity tests as possible with valid QSAR

  4. Sub-chronic toxicity study of a novel herbal-based formulation (Semelil on dogs

    Directory of Open Access Journals (Sweden)

    Farzamfar B

    2008-04-01

    Full Text Available Semelil (ANGIPARSTM, a novel herbal-based compound containing extract of Melilotus officinalis, was formulated for treatment of chronic wounds, especially diabetic foot ulcer. The purpose of this study was to investigate safety and toxicity effects of intramuscular administration of Semelil in dogs. "nPreliminary one-month study with Semelil was performed on 8 male and female dogs divided into 2 groups, test and control, four animals each. Semelil was administered intramuscularlyat a dose of 0.07 ml/kg body wt. once a day to the animals of the test group, while the control group received sterile saline. During experiments, general state of the animals including the dynamics of body weight changes, appetite, motor activity and behavior, hair condition, ECG parameters, rectal temperature of animals and data of hematological and biochemical tests were monitored for signs of toxicity and side-effects. Finally, morphology and histology analyses were performed using standard methods."nNo adverse health or toxicity effects were observed through the course of the study. No damaging consequences of Semelil injections on the functional state of main organs of the experimental animals were found. This observation gave a good evidence of a favorable safety profile compatible with potential therapeutic use of Semelil.

  5. Introducing Toxics

    Directory of Open Access Journals (Sweden)

    David C. Bellinger

    2013-04-01

    Full Text Available With this inaugural issue, Toxics begins its life as a peer-reviewed, open access journal focusing on all aspects of toxic chemicals. We are interested in publishing papers that present a wide range of perspectives on toxicants and naturally occurring toxins, including exposure, biomarkers, kinetics, biological effects, fate and transport, treatment, and remediation. Toxics differs from many other journals in the absence of a page or word limit on contributions, permitting authors to present their work in as much detail as they wish. Toxics will publish original research papers, conventional reviews, meta-analyses, short communications, theoretical papers, case reports, commentaries and policy perspectives, and book reviews (Book reviews will be solicited and should not be submitted without invitation. Toxins and toxicants concern individuals from a wide range of disciplines, and Toxics is interested in receiving papers that represent the full range of approaches applied to their study, including in vitro studies, studies that use experimental animal or non-animal models, studies of humans or other biological populations, and mathematical modeling. We are excited to get underway and look forward to working with authors in the scientific and medical communities and providing them with a novel venue for sharing their work. [...

  6. Neurotoxicity of 1-bromopropane: Evidence from animal experiments and human studies

    Directory of Open Access Journals (Sweden)

    Gaku Ichihara

    2012-04-01

    Full Text Available 1-Bromopropane was introduced as an alternative to ozone layer-depleting solvents such as chlorofluorocarbons and 1,1,1-trichloroethane. However, a dozen human cases have been reported with symptoms and signs of toxicity to 1-bromopropane including numbness, diminished vibration sense in the lower extremities as well as ataxic gait. An epidemiological study also demonstrated dose-dependent prolongation of distal latency and decrease in vibration sense in the lower extremities. The initial animal experiments helped to identify and analyze the initial human case of 1-bromopropane toxicity. However, animal data that can explain the central nervous system disorders in humans are limited. Nonetheless, animal data should be carefully interpreted especially in a high-order function of the central nervous system or neurological signs such as ataxia that is influenced by fundamental anatomical/physiological differences between humans and animals. Enzymatic activity in the liver may explain partly the difference in the susceptibility between humans and animals, but further studies are needed to clarify the biological factors that can explain the difference and commonality among the species.

  7. Acute silver toxicity in aquatic animals is a function of sodium uptake rate

    DEFF Research Database (Denmark)

    Bianchini, A.; Grosell, Martin Hautopp; Gregory, S.

    2002-01-01

    -specific surface area of the gills depends on animal body mass; and (iv) the gill surface is also the major site of Na+ loss by diffusion, we hypothesized that whole body Na+ uptake rate (i.e., turnover rate) and secondarily body mass would be good predictors of acute silver toxicity. Results obtained from...... toxicological (LC50 of AgNO3) and physiological (22Na uptake rate) tests performed on juvenile fish (rainbow trout, Oncorhynchus mykiss), early juvenile and adult crayfish (Cambarus diogenes diogenes), and neonate and adult daphnids (Daphnia magna) in moderately hard water of constant quality support the above...... hypothesis. Therefore, sensitivity to AgNO3, in terms of either total measured silver or free Ag+, was reliably predicted from the whole body Na+ uptake rate in animals with body mass ranging over 6 orders of magnitude (from micrograms to grams). A positive log-log correlation between acute AgNO3 toxicity...

  8. Histological vis-a-vis biochemical assessment on the toxic level and antineoplastic efficacy of a synthetic drug Pt-ATP on experimental animal models.

    Science.gov (United States)

    Pal, Shipra; Sadhu, Arpita Sengupta; Patra, Swarup; Mukherjea, Kalyan K

    2008-11-12

    Cisplatin, a platinum based anticancer drug has played a vital role in the treatment of cancers by chemical agents, but in view of the serious toxicity including nephrotoxicity of cisplatin, various other platinum based drugs have been synthesized and screened to overcome its toxicity. A Pt-ATP compound was prepared in our laboratory hoping to have reduced or no toxicity along with the potentiality of reducing neoplasm growth. A Pt-ATP compound was prepared. It was first screened for its antineoplastic efficacy. Confirming that, subsequent experiments were carried on to test its toxicity on animals, viz. Albino Swiss mice. The animals were randomly divided into four sets--Set I: Erhlich Ascites Carcinoma (EAC) challenged mice; Set II: Normal mice; Set III: Drug treated mice, Set IVA Cisplatin (CDDP) treated mice, Set IV B EAC challenged Cisplatin treated mice. Set I was used to test antineoplasticity of the drug, Set II and Set III for studying drug toxicity and Set IV was treated with CDDP. Set II was used as a control. Animals were sacrificed after 5 days, 10 days 15 days and 20 days of drug administration on the 6th, 11th, 16th and 21st days respectively for Set I, II and III. Set IVA was sacrificed only on the 16th day and Set IV B on 6th and 11th days. For Set I only tumor cell count and packed cell volume (PCV) of tumor cells were recorded. For Set II and III, aspartate aminotransferase (AST), alanine aminotransferase (ALT) assays were done using serum while blood creatinine and creatine were assayed from blood filtrate. For cytotoxicity assessment liver, spleen and kidney tissues were collected and subjected to scanning electron microscopy (SEM) after extensive treatment. Set IV A was only studied for the biochemical parameters viz. aspartate aminotransferase (AST), alanine aminotransferase (ALT) assays were done using serum while blood creatinine and creatine were assayed from blood filtrate. Set IV B was studied for tumor cell count after treatment with

  9. The putative multidrug resistance protein MRP-7 inhibits methylmercury-associated animal toxicity and dopaminergic neurodegeneration in Caenorhabditis elegans.

    Science.gov (United States)

    VanDuyn, Natalia; Nass, Richard

    2014-03-01

    Parkinson's disease (PD) is the most prevalent neurodegenerative motor disorder worldwide, and results in the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta. Gene-environment interactions are believed to play a significant role in the vast majority of PD cases, yet the toxicants and the associated genes involved in the neuropathology are largely ill-defined. Recent epidemiological and biochemical evidence suggests that methylmercury (MeHg) may be an environmental toxicant that contributes to the development of PD. Here, we report that a gene coding for the putative multidrug resistance protein MRP-7 in Caenorhabditis elegans modulates whole animal and DA neuron sensitivity to MeHg. In this study, we demonstrate that genetic knockdown of MRP-7 results in a twofold increase in Hg levels and a dramatic increase in stress response proteins associated with the endoplasmic reticulum, golgi apparatus, and mitochondria, as well as an increase in MeHg-associated animal death. Chronic exposure to low concentrations of MeHg induces MRP-7 gene expression, while exposures in MRP-7 genetic knockdown animals results in a loss of DA neuron integrity without affecting whole animal viability. Furthermore, transgenic animals expressing a fluorescent reporter behind the endogenous MRP-7 promoter indicate that the transporter is expressed in DA neurons. These studies show for the first time that a multidrug resistance protein is expressed in DA neurons, and its expression inhibits MeHg-associated DA neuron pathology. © 2013 International Society for Neurochemistry.

  10. Safety studies of homoeopathic drugs in acute, sub-acute and chronic toxicity in rats

    Directory of Open Access Journals (Sweden)

    Surender Singh

    2017-01-01

    Full Text Available Background: Homoeopathic drugs are frequently recommended in day to day life as therapeutic agents by homoeopathic practitioners. However, safety of homoeopathic drugs remains a challenge because of the high variability of chemical components involved. Aim: The objective of the present study was to investigate the acute, subacute, and chronic oral toxicity of different homoeopathic drugs (Ferrum phosphoricum 3X, Ferrum phosphoricum 6X, Calcarea phosphoricum 6X, and Magnesium phosphoricum 6X in experimental models. Materials and Methods: In acute oral toxicity study, homoeopathic drugs were administered orally at 2000mg/kg body weight, and animals were observed for toxic symptoms till 10 days as per the OECD guidelines. For subacute and chronic toxicity study, homoeopathic drugs were administered for 28 and 180 days, respectively, as per the OECD guidelines. At the end of 28 and 180 days, the animals were sacrificed and toxicity parameters were assessed. Histopathological evaluation of different organs was also performed to assess any toxicity. Results: In acute toxicity study, no mortality was found at a dose of 2000 mg/kg which indicates that oral LD50of homoeopathic drugs were more than 2000 mg/kg. The administration of drugs at a dose of 70 mg/kg body weight for 28 and 180 days did not produce any significant change in haematological and biochemical parameters of male and female rats as compared to normal control group. No pathological changes were observed in histology of various organs of treated rats as compared to normal control animals. Conclusion: These homoeopathic drugs are safe & produce no toxicity when administered for longer duration.

  11. A Roadmap for the Development of Alternative (Non-Animal) Methods for Systemic Toxicity Testing

    Science.gov (United States)

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new prod...

  12. The influence of salinity on copper accumulation and its toxic effects in estuarine animals with differing osmoregulatory strategies.

    Science.gov (United States)

    Lee, Jacqueline A; Marsden, Islay D; Glover, Chris N

    2010-08-01

    Copper is an important ionoregulatory toxicant in freshwater, but its effects in marine and brackish water systems are less well characterised. The effect of salinity on short-term copper accumulation and sublethal toxicity in two estuarine animals was investigated. The osmoregulating crab Hemigrapsus crenulatus accumulated copper in a concentration-dependent, but salinity-independent manner. Branchial copper accumulation correlated positively with branchial sodium accumulation. Sublethal effects of copper were most prevalent in 125% seawater, with a significant increase in haemolymph chloride noted after 96h at exposure levels of 510 microg Cu(II) L(-1). The osmoconforming gastropod, Scutus breviculus, was highly sensitive to copper exposure, a characteristic recognised previously in related species. Toxicity, as determined by a behavioural index, was present at all salinities and was positively correlated with branchial copper accumulation. At 100% seawater, increased branchial sodium accumulation, decreased haemolymph chloride and decreased haemolymph osmolarity were observed after 48h exposure to 221 microg Cu(II) L(-1), suggesting a mechanism of toxicity related to ionoregulation. However, these effects were likely secondary to a general effect on gill barrier function, and possibly mediated by mucus secretion. Significant impacts of copper on haemocyanin were also noted in both animals, highlighting a potentially novel mechanism of copper toxicity to animals utilising this respiratory pigment. Overall these findings indicate that physiology, as opposed to water chemistry, exerts the greatest influence over copper toxicity. An understanding of the physiological limits of marine and estuarine organisms may be critical for calibration of predictive models of metal toxicity in waters of high and fluctuating salinities. Copyright 2010 Elsevier B.V. All rights reserved.

  13. Functional aspects of developmental toxicity of polyhalogenated aromatic hydrocarbons in experimental animals and human infants

    NARCIS (Netherlands)

    Brouwer, A.; Ahlborg, U. G.; van den Berg, M.; Birnbaum, L. S.; Boersma, E. R.; Bosveld, B.; Denison, M. S.; Gray, L. E.; Hagmar, L.; Holene, E.

    1995-01-01

    A scientific evaluation was made of functional aspects of developmental toxicity of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in experimental animals and in human infants. Persistent neurobehavioral, reproductive and

  14. Acute and subchronic oral toxicity studies in rats of a hydrolyzed chicken sternal cartilage preparation.

    Science.gov (United States)

    Schauss, A G; Merkel, D J; Glaza, S M; Sorenson, S R

    2007-02-01

    Two acute and subchronic oral toxicity studies were conducted in rats to evaluate safety of a patented preparation of hydrolyzed chicken sternal cartilage (BioCell Collagen II) containing collagen type II, chondroitin sulfate, and hyaluronic acid. In the acute oral toxicity study, five males and five females of Sprague-Dawley rats were administered a single dose of 5000 mg of the test product per kg body weight and observed for 14 days. All animals survived and exhibited normal body weight gain throughout the study. Macroscopic necropsy examination conducted on day 15 revealed no gross pathological lesions in any of the animals. In the subchronic study, Sprague-Dawley rats (40 males, 40 females) were divided into four same-sex groups (10 animals/group). Animals in each group were administered daily either 0, 30, 300 or 1000 mg of the test product per kg of body weight for over 90 days. All animals survived and showed no significant changes in their body weights and histopathology. Although some differences were observed between the treated and control animals in several parameters, they were generally not dose-related or considered to be of toxicological significance. In conclusion, the results from the two oral toxicity studies with male and female young adult rats indicated that the test preparation from hydrolyzed chicken sternal cartilage collagen (BioCell Collagen II) was well tolerated at all four doses tested.

  15. Acute and sub-chronic toxicity studies of honokiol microemulsion.

    Science.gov (United States)

    Zhang, Qianqian; Li, Jianguo; Zhang, Wei; An, Quan; Wen, Jianhua; Wang, Aiping; Jin, Hongtao; Chen, Shizhong

    2015-04-01

    The purpose of this study was to investigate the acute and sub-chronic toxicity of honokiol microemulsion. In the acute toxicity tests, the mice were intravenously injected graded doses of honokiol microemulsion and were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were injected honokiol microemulsion at doses of 100, 500, 2500 μg/kg body weight (BW) for 30 days. After 30 days treatment and 14 days recovery, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD50) was 50.5mg/kg body weight in mice. In the sub-chronic toxicity tests, the non-toxic reaction dose was 500 μg/kg body weight. In each treatment group, degeneration or/and necrosis in vascular endothelial cells and structure change of vessel wall can be observed in the injection site (cauda vein) of a few animals while there were no changes in the vessels of other organs. The overall findings of this study indicate that the honokiol microemulsion is non-toxic up to 500 μg/kg body weight, and it has irritation to the vascular of the injection site which should be paid attention to in clinical medication. Copyright © 2015. Published by Elsevier Inc.

  16. Cellulose/soy protein isolate composite membranes: evaluations of in vitro cytocompatibility with Schwann cells and in vivo toxicity to animals.

    Science.gov (United States)

    Luo, Lihua; Gong, Wenrong; Zhou, Yi; Yang, Lin; Li, Daokun; Huselstein, Celine; Wang, Xiong; He, Xiaohua; Li, Yinping; Chen, Yun

    2015-01-01

    To evaluate the in vitro cytocompatibility of cellulose/soy protein isolate composite membranes (CSM) with Schwann cells and in vivo toxicity to animals. A series of cellulose/soy protein isolate composite membranes (CSM) were prepared by blending, solution casting and coagulation process. The cytocompatibility of the CSM to Schwann cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and by direct cells culture of Schwann cells on the surfaces of the CSM, respectively. The in vivo toxicity of the CSM to animals were also evaluated by acute toxicity testing, skin sensitization testing, pyrogen testing and intracutaneous stimulation testing, respectively, according to the ISO 10993 standard. The MTT assay showed that the cell viability of Schwann cells cultured in extracts from the CSM was higher than that from the neat cellulose membrane without containing SPI component. The direct cells culture indicated that the Schwann cells could attach and grow well on the surface of the CSM and the incorporation of SPI into cellulose contributed to improvement of cell adhesion and proliferation. The evaluations of in vivo biological safety suggested that the CSM showed no acute toxicity, no skin sensitization and no intracutaneous stimulation to the experimental animals. The CSM had in vitro cytocompatibility with Schwann cells and biological safety to animals, suggesting potential for the applications as nerve conduit for the repair of nerve defect.

  17. [Advance in study on zearalenone's toxicity and determination].

    Science.gov (United States)

    He, Qing-Hua; Xu, Yang

    2005-07-01

    The article is intended to introduce the zearalenone's toxicity, determination methods and prevention. Zearalenone is one of the most widely distributed mycotoxins produces by Fusarium Species, it is harm to animals and human. And it can induce human liver cancer,carcinoma of tesis esophagus cancer. Now we use high-performance liquid chromatography, gas chromatography, thin layer chromatography, non-toxicity determinations to detect it.

  18. Application of Neutron Activation Analysis to the determination of essential and toxic elements in agroindustrial by-products employed in animal feeding

    International Nuclear Information System (INIS)

    Teruya, Carla Mitie

    1999-01-01

    In the present work the concentrations of essential elements Ca (calcium), CI (chlorine), K (potassium), Mg (magnesium), Na (sodium), Co (cobalt), Cr (chromium), Cu (copper), Fe (iron), Mn (manganese). Mo (molybdenum), Se (selenium), V (vanadium) and Zn (zinc), the toxic elements As (arsenic), Cd (cadmium) and Hg (mercury) and the elements without defined functions to the animal metabolism, such as Br (bromine), Eu (europium). La (lanthanum), Rb (rubidium), Sb (antinomies), Sc (scandium), Ta (tantalum), Th (thorium) and U (uranium) were determined in agroindustrial by-products employed in animal feeding by instrumental neutron activation analysis (INAA). Forty samples of agroindustrial by-products were analyzed, six of which are from animal origin and the others are from vegetable origin. All these materials are widely used in bovine feeding, mainly in dry season, when the forage become scarce. The precision and accuracy of the method were evaluated by means of analysis of the following certified reference materials: Rice Flour NIES-CRM-10C, Pig Kidney BCR-CRM, Oyster Tissue NIST-SRM-1566a e Buffalo River Sediment NIST-SRM-2704. The results, in general, are lower than 10 %. The results for the most of essential minerals were lower than the toxic limit for animals, and they reached the minimum requirements for domestic animals, although some agroindustrial by-products showed concentrations lower than the requirement. For all samples, the concentrations of toxic minerals were lower than the toxic limit (author)

  19. Characterizing interspecies uncertainty using data from studies of anti-neoplastic agents in animals and humans

    International Nuclear Information System (INIS)

    Price, Paul S.; Keenan, Russell E.; Swartout, Jeffrey C.

    2008-01-01

    For most chemicals, the Reference Dose (RfD) is based on data from animal testing. The uncertainty introduced by the use of animal models has been termed interspecies uncertainty. The magnitude of the differences between the toxicity of a chemical in humans and test animals and its uncertainty can be investigated by evaluating the inter-chemical variation in the ratios of the doses associated with similar toxicological endpoints in test animals and humans. This study performs such an evaluation on a data set of 64 anti-neoplastic drugs. The data set provides matched responses in humans and four species of test animals: mice, rats, monkeys, and dogs. While the data have a number of limitations, the data show that when the drugs are evaluated on a body weight basis: 1) toxicity generally increases with a species' body weight; however, humans are not always more sensitive than test animals; 2) the animal to human dose ratios were less than 10 for most, but not all, drugs; 3) the current practice of using data from multiple species when setting RfDs lowers the probability of having a large value for the ratio. These findings provide insight into inter-chemical variation in animal to human extrapolations and suggest the need for additional collection and analysis of matched toxicity data in humans and test animals

  20. Application of a novel integrated toxicity testing strategy incorporating "3R" principles of animal research to evaluate the safety of a new agrochemical sulfoxaflor.

    Science.gov (United States)

    Terry, Claire; Rasoulpour, Reza J; Saghir, Shakil; Marty, Sue; Gollapudi, B Bhaskar; Billington, Richard

    2014-05-01

    Plant protection products (PPPs) and the active substance(s) contained within them are rigorously and comprehensively tested prior to registration to ensure that human health is not impacted by their use. In recent years, there has been a widespread drive to have more relevant testing strategies (e.g., ILSI/HESI-ACSA and new EU Directives), which also take account of animal welfare, including the 3R (replacement, refinement, and reduction) principles. The toxicity potential of one such new active substance, sulfoxaflor, a sulfoximine insecticide (CAS #946578-00-3), was evaluated utilizing innovative testing strategies comprising: (1) an integrated testing scheme to optimize information obtained from as few animals as possible (i.e., 3R principles) through modifications of standard protocols, such as enhanced palatability study design, to include molecular endpoints, additional neurotoxicity and immunotoxicity parameters in a subchronic toxicity study, and combining multiple test guidelines into one study protocol; (2) generation of toxicokinetic data across dose levels, sexes, study durations, species, strains and life stages, without using satellite animals, which was a first for PPP development, and (3) addition of prospective mode of action (MoA) endpoints within repeat dose toxicity studies as well as proactive inclusion of specific MoA studies as an integral part of the development program. These novel approaches to generate key data early in the safety evaluation program facilitated informed decision-making on the need for additional studies and contributed to a more relevant human health risk assessment. This supplement also contains papers which describe in more detail the approach taken to establish the MoA and human relevance framework related to toxicities elicited by sulfoxaflor in the mammalian toxicology studies: developmental toxicity in rats mediated via the fetal muscle nicotinic acetylcholine receptor (nAChR) ( Ellis-Hutchings et al. 2014 ); liver

  1. Sacha Inchi (Plukenetia volubilis L. powder: acute toxicity, 90 days oral toxicity study and micronucleus assay in rodents

    Directory of Open Access Journals (Sweden)

    Idania Rodeiro

    2018-02-01

    Full Text Available Context: Sacha Inchi has been consumed for years by indigenous peoples. Meanwhile, its toxicological potential has not been sufficiently studied. Aims: To assess the acute, sub-chronic toxicity and genotoxicity evaluation of Sacha Inchi powder obtained from Plukenetia volubilis L. Methods: A dose of 2000 mg/kg was orally administered to rats and mice and toxicity symptoms for 14 days were observed. In repeated dose study, the product was orally administered to Sprague Dawley rats of both sexes. Animals received 50, 250 and 500 mg/kg/day of the product for 90 days. At the end, animals were sacrificed and samples were done for hematological and biochemical analysis, organ weighs and histopathological examination. Genotoxicity potential of Sacha Inchi powder was evaluated through micronucleus test in mice. Negative controls received the vehicle (carboxymethyl cellulose, 0.5% used. Results: No morbidity or mortality at 2000 mg/kg of the product were found. Sacha Inchi powder oral administration during 90 days to rats did not lead to death, body weight gain, food consumption, or adverse events. No significant changes on hematological or biochemical parameters, organ weights or histopathological findings were observed. Induction of micronucleus formation attributable to the product was not found in mice. Conclusions: No toxicity effects after oral acute exposure of Sacha Inchi power to rats and mice were observed. Neither toxicity attributable to oral doses of the product up to 500 mg/kg during 90 days to rats were found. Results suggested Sacha Inchi powder does not have genotoxicity potential under our experimental conditions.

  2. Acute and 28-day subchronic toxicity studies of mangiferin, a glucosylxanthone isolated from Mangifera indica L. stem bark.

    Directory of Open Access Journals (Sweden)

    Yalena Prado

    2015-02-01

    Full Text Available Context: Pharmacological properties of mangiferin have been reported, but few studies have investigated mangiferin toxicity. Aims: To study the acute and 28-day toxicity effects of mangiferin in rodents. Methods: Single doses of mangiferin were administered by oral or i.p. route or were applied dermally to Sprague-Dawley rats and Balb/C mice. Clinical symptoms of animals were observed during 14 days after treatment. Animals also received single oral doses daily for 28 consecutive days. Blood biochemistry, hematology and pathology findings were reported. Results: In the acute study, no toxic effects were observed after dermal exposure to mangiferin 2000 mg/kg but transient dyspnea, flank position and piloerection were observed after oral administration to this xanthone. I.p. administration induced similar toxicity signs, but at the highest dose (2000 mg/kg all mice, one female rat and one male rat died. Rats orally treated with mangiferin (250-1000 mg/kg for 28 days did not show any abnormal clinical signs or hematology alterations, when compared to control group animals. Histopathological alterations like vacuolar degeneration, necrosis and increment of apoptosis of the acinar cells were observed in the exocrine pancreas of rats at 1000 mg/kg. This suggesting that exocrine pancreas was the target organ for mangiferin’s toxicity. Conclusions: These studies indicated that acute and subchronic toxicities of mangiferin for oral exposure are low.

  3. A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report

    OpenAIRE

    Basketter, D.A.; Clewell, H.; Kimber, I.; Rossi, A.; Blaauboer, B.J.; Burrier, R.; Daneshian, M.; Eskes, C.; Goldberg, A.; Hasiwa, N.

    2012-01-01

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds esp...

  4. Studies on toxicity, anti-stress and hepato-protective properties of Kombucha tea.

    Science.gov (United States)

    Pauline, T; Dipti, P; Anju, B; Kavimani, S; Sharma, S K; Kain, A K; Sarada, S K; Sairam, M; Ilavazhagan, G; Devendra, K; Selvamurthy, W

    2001-09-01

    The objective of the study was to evaluate toxicity, anti-stress activity and hepato-protective properties of Kombucha tea. Kombucha tea was fed orally for 15 days using three different doses i.e. normal dose, five and ten times the dose. Rats were then sacrificed and various biochemical, and histological parameters were estimated. Anti-stress activity was evaluated either by 1) by exposing animals to cold and hypoxia and estimating the levels of malondialdehyde and reduced glutathione in plasma/blood or 2) by subjecting the animals to restraint stress and recording faecal output. Hepato-toxicity was induced by challenging the animals to an acute dose of paracetamol (1 gm/kg) orally and determining the plasma levels of SGPT, SGOT and MDA. The effect of oral administration of different doses of K-tea to albino rats was examined and the results indicate that K-tea has no significant toxicity as revealed by various biochemical and histopathological parameters. K-tea has been found to prevent lipid peroxidation and fall in reduced glutathione level when rats were exposed to cold and hypoxia in simulated chamber. Further, K-tea has also been found to decrease the Wrap-restraint faecal pellet output in rats. K-tea has also been found to decrease paracetamol induced hepatotoxicity significantly. The study shows that K-tea has anti-stress and hepato-protective activities.

  5. Subacute (90 days) oral toxicity studies of Kombucha tea.

    Science.gov (United States)

    Vijayaraghavan, R; Singh, M; Rao, P V; Bhattacharya, R; Kumar, P; Sugendran, K; Kumar, O; Pant, S C; Singh, R

    2000-12-01

    Kombucha tea (KT) is a popular health beverage and is used as an alternative therapy. KT is prepared by placing the kombucha culture in solution of tea and sugar and allowing to ferment. The inoculum is a fungus consisting of symbiotic colony of yeast and bacteria. KT is consumed in several countries and is believed to have prophylactic and therapeutic benefits in a wide variety of ailments, viz., intestinal disorders, arthritis, ageing and stimulation of immunological system. Though KT is used in several parts of the world its beneficial effects and adverse effects have not been scientifically evaluated. Since there are no animal toxicological data on KT, subacute oral toxicity study was carried out. Five groups of rats were maintained: (a) control group given tap water orally, (b) KT given 2 ml/kg orally, (c) plain tea (PT) given 2 ml/kg orally, (d) KT given in drinking water, 1% (v/v) and (e) PT given in drinking water, 1% (v/v). The rats were given this treatment daily for a period of 90 days. Weekly records of weight, feed intake, water intake and general behaviour were monitored. There was no significant difference in the growth of the animals as evidenced by the progressive body weight change. The organ to body weight ratio and histological evaluation did not show any toxic signs. The haematological and biochemical variables were within the clinical limits. The study indicates that rats fed KT for 90 days showed no toxic effects.

  6. Review of reproductive and developmental toxicity induced by organotins in aquatic organisms and experimental animals

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, A.; Takagi, A.; Nishimura, T.; Kanno, J.; Ema, M. [National Inst. of Health Sciences, Tokyo (Japan)

    2004-09-15

    Widespread use of organotins has caused increasing amounts to be released into the environment. The most important non-pesticidal route of entry of organotins into the environment is through leaching of organotin-stabilized PVC in water, and the use in antifouling agents, resulting in the introduction of organotin into the aquatic environment. Data are available regarding the detection of butyltins and phenyltins in aquatic marine organisms and marine products. Food chain bioamplification of butyltin in oysters, mud crabs, marine mussels, chinook salmons, dolphins, tunas, and sharks and of phenyltin in carps and horseshoe crabs has been reported. These findings indicate that organotins accumulate in the food chain and are bioconcentrated, and that humans can be exposed to organotins via seafood. The levels of organotin compounds in seafood are not considered to be sufficiently high to affect human health. However, Belfroid et al. (2000) noted that more research on residual TBT levels in seafood was needed before a definitive conclusion on possible health risks could be drawn. Although the toxicity of organotins has been extensively reviewed, the reproductive and developmental toxicity of organotins is not well understood. We summarized the data of the studies on reproductive and developmental toxicity of organotins in aquatic organisms and experimental animals.

  7. Developmental toxicity of organotin compounds in animals

    Directory of Open Access Journals (Sweden)

    Lijiao eWu

    2014-09-01

    Full Text Available Organotin compounds (OTs have been used as biocides in antifouling paints and agriculture. The IMO introduced a global ban on the use of OTs in antifouling systems in 2001 due to their high toxicity. However, OTs have still been detected in the environment and pose a threat to the ecosystem. Several research groups have summarized the analytical methods, environmental fate, biochemistry, reproductive toxicity and mechanisms of actions of OTs. Here, we reviewed the developmental toxicity of OTs in various organisms such as sea urchin, ascidian, mussel and fish. The differences in sensitivity to OT exposure exist not only in different species but also at different stages in the same species. Though some hypotheses have been proposed to explain the developmental toxicity of OTs, the solid evidences are greatly in need.

  8. A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report

    NARCIS (Netherlands)

    Basketter, D.A.; Clewell, H.; Kimber, I.; Rossi, A.; Blaauboer, B.J.; Burrier, R.; Daneshian, M.; Eskes, C.; Goldberg, A.; Hasiwa, N.

    2012-01-01

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as

  9. The use of whole food animal studies in the safety assessment of genetically modified crops: Limitations and recommendations

    Science.gov (United States)

    Bartholomaeus, Andrew; Parrott, Wayne; Bondy, Genevieve

    2013-01-01

    There is disagreement internationally across major regulatory jurisdictions on the relevance and utility of whole food (WF) toxicity studies on GM crops, with no harmonization of data or regulatory requirements. The scientific value, and therefore animal ethics, of WF studies on GM crops is a matter addressable from the wealth of data available on commercialized GM crops and WF studies on irradiated foods. We reviewed available GM crop WF studies and considered the extent to which they add to the information from agronomic and compositional analyses. No WF toxicity study was identified that convincingly demonstrated toxicological concern or that called into question the adequacy, sufficiency, and reliability of safety assessments based on crop molecular characterization, transgene source, agronomic characteristics, and/or compositional analysis of the GM crop and its near-isogenic line. Predictions of safety based on crop genetics and compositional analyses have provided complete concordance with the results of well-conducted animal testing. However, this concordance is primarily due to the improbability of de novo generation of toxic substances in crop plants using genetic engineering practices and due to the weakness of WF toxicity studies in general. Thus, based on the comparative robustness and reliability of compositional and agronomic considerations and on the absence of any scientific basis for a significant potential for de novo generation of toxicologically significant compositional alterations as a sole result of transgene insertion, the conclusion of this review is that WF animal toxicity studies are unnecessary and scientifically unjustifiable. PMID:24164514

  10. The use of whole food animal studies in the safety assessment of genetically modified crops: limitations and recommendations.

    Science.gov (United States)

    Bartholomaeus, Andrew; Parrott, Wayne; Bondy, Genevieve; Walker, Kate

    2013-11-01

    There is disagreement internationally across major regulatory jurisdictions on the relevance and utility of whole food (WF) toxicity studies on GM crops, with no harmonization of data or regulatory requirements. The scientific value, and therefore animal ethics, of WF studies on GM crops is a matter addressable from the wealth of data available on commercialized GM crops and WF studies on irradiated foods. We reviewed available GM crop WF studies and considered the extent to which they add to the information from agronomic and compositional analyses. No WF toxicity study was identified that convincingly demonstrated toxicological concern or that called into question the adequacy, sufficiency, and reliability of safety assessments based on crop molecular characterization, transgene source, agronomic characteristics, and/or compositional analysis of the GM crop and its near-isogenic line. Predictions of safety based on crop genetics and compositional analyses have provided complete concordance with the results of well-conducted animal testing. However, this concordance is primarily due to the improbability of de novo generation of toxic substances in crop plants using genetic engineering practices and due to the weakness of WF toxicity studies in general. Thus, based on the comparative robustness and reliability of compositional and agronomic considerations and on the absence of any scientific basis for a significant potential for de novo generation of toxicologically significant compositional alterations as a sole result of transgene insertion, the conclusion of this review is that WF animal toxicity studies are unnecessary and scientifically unjustifiable.

  11. Pulmonary Toxicity Studies of Lunar Dust in Rodents

    Science.gov (United States)

    Lam, Chiu-Wing; James, John T.

    2012-01-01

    NASA has been contemplating returning astronauts to the moon for long-duration habitation and research and using it as a stepping-stone to Mars. Other spacefaring nations are planning to send humans to the moon for the first time. The surface of the moon is covered by a layer of fine dust. Fine terrestrial dusts, if inhaled, are known to pose a health risk to humans. Some Apollo crews briefly exposed to moon dust that adhered to spacesuits and became airborne in the Lunar Module reported eye and throat irritation. The habitable area of any lunar landing vehicle or outpost would inevitably become contaminated with lunar dust. To assess the health risks of exposure of humans to airborne lunar dust, we evaluated the toxicity of Apollo 14 moon dust in animal lungs. Studies of the pulmonary toxicity of a dust are generally first done by intratracheal instillation (ITI) of aqueous suspensions of the test dust into the lungs of rodents. If a test dust is irritating or cytotoxic to the lungs, the alveolar macrophages, after phagocytizing the dust particles, will release cellular messengers to recruit white blood cells (WBCs) and to induce dilation of blood capillary walls to make them porous, allowing the WBCs to gain access to the alveolar space. The dilation of capillary walls also allows serum proteins and water entering the lung. Besides altering capillary integrity, a toxic dust can also directly kill the cells that come into contact with it or ingest it, after which the dead cells would release their contents, including lactate dehydrogenase (a common enzyme marker of cell death or tissue damage). In the treated animals, we lavaged the lungs 1 and 4 weeks after the dust instillation and measured the concentrations of these biomarkers of toxicity in the bronchioalveolar lavage fluids to determine the toxicity of the dust. To assess whether the inflammation and cellular injury observed in the biomarker study would lead to persistent or progressive histopathological

  12. Some biochemical characteristics of a toxic substance isolated from organs of lethally irradiated animals in the course of the intestinal syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Meter, J D; Sirota, N S [Tsentral' nyj Nauchno-Issledovatel' skij Rentgeno-Radiologicheskij Inst., Leningrad (USSR)

    1976-05-01

    A toxic substance isolated from organs of lethally irradiated (1300 rads) animals in the period when intestinal syndrome has developed is classified according to the parameters under study (namely, the molecular weight, UV-absorption curve, extinction coefficient, specific monosaccharides, the presence and percentage of KDA, etc.) as lipopolysaccharide of Escherichia coli, the main inhabitant of the gastroenteric tract of mice. That endotoxins (sensitivity to which is increased in this period of radiation sickness) are detected in the blood and organs of lethally irradiated animals, might indicate their participation in the pathogenesis of the intestinal syndrome.

  13. Some biochemical characteristics of a toxic substance isolated from organs of lethally irradiated animals in the course of the intestinal syndrome

    International Nuclear Information System (INIS)

    Meter, J.D.; Sirota, N.S.

    1976-01-01

    A toxic substance isolated from organs of lethally irradiated (1300 rads) animals in the period when intestinal syndrome has developed is classified according to the parameters under study (namely, the molecular weight, UV-absorption curve, extinction coefficient, specific monosaccharides, the presence and percentage of KDA, etc.) as lipopolysaccharide of Escherichia coli, the main inhabitant of the gastroenteric tract of mice. That endotoxins (sensitivity to which is increased in this period of radiation sickness) are detected in the blood and organs of lethally irradiated animals, might indicate their participation in the pathogenesis of the intestinal syndrome

  14. Oral treatment with a rattlesnake native polypeptide crotamine efficiently inhibits the tumor growth with no potential toxicity for the host animal and with suggestive positive effects on animal metabolic profile.

    Science.gov (United States)

    Campeiro, Joana D; Marinovic, Marcelo P; Carapeto, Fernando Cintra; Dal Mas, Caroline; Monte, Gabriela Guilherme; Carvalho Porta, Lucas; Nering, Marcela B; Oliveira, Eduardo B; Hayashi, Mirian A F

    2018-02-01

    The efficacy of crotamine as antitumoral was first demonstrated by daily intraperitoneal (IP) injections of low doses of this toxin in an animal model bearing melanoma tumors. Significant inhibition of tumor growth and increased lifespan of mice bearing tumor was also noticed after 21 consecutive days of this daily IP administration of crotamine. However, due to the limited acceptance of treatments by IP route in clinical conditions, herein, we evaluated the antitumor effect of this native polypeptide employing the oral route. The efficacy of crotamine in inhibiting the melanoma growth in vivo, even after passing through the gastrointestinal tract of the animal, was confirmed here. In addition, biochemical biomarkers and also histopathological analysis showed both the absence of any potential toxic effects in tissues or organs of the animal in which the highest accumulation of crotamine is expected. Interestingly, a reduction of weight gain was observed mainly in animals with tumor treated with crotamine by IP route, but not by oral administration. Albeit, oral administered crotamine was able to significantly decrease the body weight gain of healthy animals without tumor. Taking advantage of this same experimental animal models receiving crotamine by oral route, it was possible to show metabolic changes as the increased capacity of glucose clearance, which was accompanied by a reduction of the total cholesterol, and by increased high-density lipoprotein levels, both observed mainly in the absence of tumor. Triglycerides and low-density lipoprotein were also significantly decreased, but only in the absence of tumor. Taken together, these data suggest a clear trend for metabolic positive effects and mischaracterize unhealthy condition of animals, with or without tumors, treated with crotamine for 21 days. In addition, this study confirmed the efficacy of crotamine administered by oral route as antitumor agent, which besides the additional advantage of

  15. Toxicity Study of Antidiabetics Functional Drink of Piper crocatum and Cinnamomum burmannii

    Directory of Open Access Journals (Sweden)

    MEGA SAFITHRI

    2012-03-01

    Full Text Available Piper crocatum and Cinnamomum burmannii formulations is known to be a new diabetes functional drink. Thus, its toxicological profile needs to be studied. At present, the formulation was evaluated for the repeated dose toxicity study. The Sprague dawley albino rats were treated with P. crocatum and C. burmannii formulations (0, 630, 1260, and 1890 mg/kg and administered orally for a period of 28 days in albino rats. The effects on body weight, food and water consumption, organ weight, hematology, clinical biochemistry as well as histology were studied. There were no significant differences in the body weight, organ weights and feeding habits between control and treated animals. Hematological analysis showed no marked differences in any of the parameters examined in either the control or treated groups. There were no significant changes that occurred in the blood chemistry analysis including glucose, cholesterol, triglycerides, creatinine, SGPT, and SGOT in experimental animals. Pathologically, neither gross abnormalities nor histopathological changes were observed. The formulation of P. crocatum and C. burmannii was found safe in repeated dose toxicity studies.

  16. Toxicity Reference Database

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxicity Reference Database (ToxRefDB) contains approximately 30 years and $2 billion worth of animal studies. ToxRefDB allows scientists and the interested...

  17. An innovative approach to sampling complex industrial emissions for use in animal toxicity tests: application to iron casting operations.

    Science.gov (United States)

    Palmer, W G; Scholz, R C; Moorman, W J

    1983-03-01

    Sampling of complex mixtures of airborne contaminants for chronic animal toxicity tests often involves numerous sampling devices, requires extensive sampling time, and yields forms of collected materials unsuitable for administration to animals. A method is described which used a high volume, wet venturi scrubber for collection of respirable fractions of emissions from iron foundry casting operations. The construction and operation of the sampler are presented along with collection efficiency data and its application to the preparation of large quantities of samples to be administered to animals by intratracheal instillation.

  18. Accumulation and Toxicity of Superparamagnetic Iron Oxide Nanoparticles in Cells and Experimental Animals.

    Science.gov (United States)

    Jarockyte, Greta; Daugelaite, Egle; Stasys, Marius; Statkute, Urte; Poderys, Vilius; Tseng, Ting-Chen; Hsu, Shan-Hui; Karabanovas, Vitalijus; Rotomskis, Ricardas

    2016-08-19

    The uptake and distribution of negatively charged superparamagnetic iron oxide (Fe₃O₄) nanoparticles (SPIONs) in mouse embryonic fibroblasts NIH3T3, and magnetic resonance imaging (MRI) signal influenced by SPIONs injected into experimental animals, were visualized and investigated. Cellular uptake and distribution of the SPIONs in NIH3T3 after staining with Prussian Blue were investigated by a bright-field microscope equipped with digital color camera. SPIONs were localized in vesicles, mostly placed near the nucleus. Toxicity of SPION nanoparticles tested with cell viability assay (XTT) was estimated. The viability of NIH3T3 cells remains approximately 95% within 3-24 h of incubation, and only a slight decrease of viability was observed after 48 h of incubation. MRI studies on Wistar rats using a clinical 1.5 T MRI scanner were showing that SPIONs give a negative contrast in the MRI. The dynamic MRI measurements of the SPION clearance from the injection site shows that SPIONs slowly disappear from injection sites and only a low concentration of nanoparticles was completely eliminated within three weeks. No functionalized SPIONs accumulate in cells by endocytic mechanism, none accumulate in the nucleus, and none are toxic at a desirable concentration. Therefore, they could be used as a dual imaging agent: as contrast agents for MRI and for traditional optical biopsy by using Prussian Blue staining.

  19. COMPARATIVE STUDY FOR SUBCHRONIC TOXICITY OF VASELINE OIL AND GLYCELAX

    Directory of Open Access Journals (Sweden)

    A. V. Voronkov

    2016-01-01

    Full Text Available Contemporary therapeutic approaches offer a wide range of laxative agents, which are often used without a control, exceeding the regime recommended. Therefore, the comparative study for subchronic toxicity of both drugs from this group (Vaseline oil and Glycelax appears interesting.The aim of the study was the comparison of a toxic influence of 14-days application of the drugs under study.Methods. The drugs were studied in two doses: higher therapeutic, and toxic, which 10 times exceeds therapeutic dose. We used “Polispektr-8/B” electrocardiograph, BC 2800vet (Mindray hematologic veterinary analyzer, BS-380 (Mindray biochemical analyzer, CL-50 urine analyzer. After the animals autopsy we determined organs’ coefficient (heart, lungs, spleen, liver, stomach, kidneys, adrenals.Results. While studying the ECG of female rats, amplitude of R wave increased after they got Glycelax in both doses. Female rats who got Vaseline oil this index decreased at minimum dose and increased at maximum dose. After Glycelax application, male rats had an increased activity of alanine aminotransferase. After Vaseline oil application at maximum dose, female rats had alkaline phosphatase activity lowered. Female rats, which got a maximum dose of Vaseline oil had a total protein lowered. Glycelax at maximum dose increased the content of bilirubin and its fractions in male and female rats, while Vaseline oil application at maximum dose increased the content of bilirubin in female rats. Male rats which got Glycelax had hemoglobin and hematocrit level increased.Conclusion. At long-term application of Vaseline oil, animals of both genders had heart disorders with possible development of arrhythmia, hepatotoxic effect, lipid exchange dysfunction. After excessive use of Glycelax the above mentioned is added with possible hemoglobin and rheological blood properties level decrease.

  20. Role of environmental stress in the physiological response to chemical toxicants

    International Nuclear Information System (INIS)

    Gordon, C.J.

    2003-01-01

    Environmental physiology is the study of the physiological mechanisms that allow animals to cope with and adapt to changes in temperature, humidity, atmospheric pressure, and other natural factors of their physical environment. Nearly all toxicological and pharmacological studies are performed in resting (i.e., non exercising) experimental animals acclimatized to standard environmental conditions that are usually considered ideal to the animal's physiological well-being. These ideal test conditions are clearly not representative of the fluctuations in the natural environment encountered by humans and other animals on a day-to-day basis. It behooves the toxicologist, especially those interested in extrapolating experimental data from laboratory animals to humans, to consider how variations in the natural environment will alter physiological responses to toxicants. Temperature and exercise are the two most well-studied parameters in the fields of environmental physiology and toxicology. In general, high temperatures exacerbate the toxic effects of many environmental toxicants. Moreover, exercising subjects are generally more vulnerable to airborne toxic agents. The prospect of global warming also warrants a better assessment of how higher environmental temperatures may impact on the response of humans and other species to toxic chemicals. Hence, this paper and accompanying papers from the proceedings of a symposium focus on the salient aspects of the interaction between environmental stress and physiological response to toxic agents with particular emphasis on temperature and exercise

  1. [Toxicity studies of landiolol hydrochloride (ONO-1101) (1). Single intravenous toxicity study in rats and dogs].

    Science.gov (United States)

    Yamaguchi, K; Kasahara, T; Yanagisawa, Y; Nanba, T; Aze, Y; Shinomiya, K; Yonezawa, H; Fujita, T

    1997-12-01

    Single dose toxicity studies of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, were conducted in Sprague-Dawley (SD) rats and beagle dogs. ONO-1101 was administered intravenously at a dose level of 37.5, 75, 150 or 300 mg/kg to rats of both sexes and 25, 50 or 100 mg/kg to male dogs. In the rat study, 5/6 males in the 150 mg/kg group and all animals in the 300 mg/kg group died during or right after administration. Survivors in the 150 mg/kg group showed temporal hypoactivity, bradypnea, dyspnea, tremor, loss of righting reflex and reddish lacrimation up to 5 min after injection. One male in the 150 mg/kg group had a tendency of suppression on body weight gain. No effects on clinical signs and body weight gain were seen in the 75 mg/kg group or lower. Necropsy findings showed only red tear in the majority of the decedents. In the dog study, all animals died within 6 min after administration in the 100 mg/kg group, showed ataxic gait, rolling and tachypnea followed by bradypnea and gasping/apnea. Incontinence of urine, defecation and vocalization were also seen in each one of two animals before death. Temporal hypoactivity was seen 1 min after administration in the 50 mg/kg group. No clinical signs were seen in the 25 mg/kg group. ONO-1101 did not affect bodyweight or food consumption. Necropsy findings of the decedents showed no abnormalities. It is indicated that the minimum lethal doses are 150 mg/kg in rats and 100 mg/kg in dogs.

  2. 90-Day oral toxicity study of D-tagatose in rats.

    Science.gov (United States)

    Kruger, C L; Whittaker, M H; Frankos, V H; Trimmer, G W

    1999-04-01

    D-tagatose is a ketohexose, tastes like sugar and is useful as a low-calorie sweetener. To assess D-tagatose's safety, an oral 90-day toxicity study was conducted on male and female Crl:CDBR rats at dietary doses of 5, 10, 15, and 20% D-tagatose. One control group (dietary control) received only lab chow; a second control group received 20% cellulose/fructose in the diet. There were no treatment-related effects at 5% D-tagatose in the diet. At higher doses, treatment-related effects included transient soft stools in male and female animals from the 15 and 20% dose groups. This was anticipated as a result of the osmotic effect of a large dose of relatively undigested sugar and was not considered a toxic effect. All treatment groups gained weight over the study period; however, mean body weights were statistically significantly decreased in the 15 and 20% dose-group males and the 20% dose-group females at selected intervals compared to dietary control animals. No significant reduction in mean food consumption was noted in the treatment groups compared to the dietary control. Statistically significantly increased relative liver weights were noted in male and female animals from the 10, 15, and 20% dose groups compared to the dietary control. No gross pathological findings correlated with these increased liver weights. Minimal hepatocellular hypertrophy was observed in male and female animals from the 15 and 20% dose groups. An independent review of the liver slides concluded that histomorphologic changes associated with D-tagatose were restricted hepatocyte hypertrophy and hepatocyte glycogen accumulation. Therefore, it was concluded that increased liver weights and minimal hypertrophy were the result of adaptation to the high dietary levels (greater than 5% in the diet) of D-tagatose. No adverse effects were seen at 5% D-tagatose in the diet. Copyright 1999 Academic Press.

  3. Examining the antimicrobial activity and toxicity to animal cells of different types of CO-releasing molecules.

    Science.gov (United States)

    Nobre, Lígia S; Jeremias, Hélia; Romão, Carlos C; Saraiva, Lígia M

    2016-01-28

    Transition metal carbonyl complexes used as CO-releasing molecules (CORMs) for biological and therapeutic applications may exhibit interesting antimicrobial activity. However, understanding the chemical traits and mechanisms of action that rule this activity is required to establish a rationale for the development of CORMs into useful antibiotics. In this work the bactericidal activity, the toxicity to eukaryotic cells, and the ability of CORMs to deliver CO to bacterial and eukaryotic cells were analysed for a set of seven CORMs that differ in the transition metal, ancillary ligands and the CO release profile. Most of these CORMs exhibited bactericidal properties that decrease in the following order: CORM-2 > CORM-3 > ALF062 > ALF850 > ALF186 > ALF153 > [Fe(SBPy3)(CO)](BF4)2. A similar yet not entirely coincident decreasing order was found for their induction of intracellular reactive oxygen species (ROS) in E. coli. In contrast, studies in model animal cells showed that for any given CORM, the level of intracellular ROS generated was negligible when compared with that measured inside bacteria. Importantly, these CORMs were in general not toxic to eukaryotic cells, namely murine macrophages, kidney LLC-PK1 epithelial cells, and liver cell line HepG2. CORM-2 and CORM-3 delivered CO to the intracellular space of both E. coli and the two types of tested eukaryotic cells, yet toxicity was only elicited in the case of E. coli. CO delivered by ALF186 into the intercellular space did not enter E. coli cells and the compound was not toxic to either bacteria or to eukaryotic cells. The Fe(ii) carbonyl complex [Fe(SBPy3)(CO)](2+) had the reverse, undesirable toxicity profile, being unexpectedly toxic to eukaryotic cells and non-toxic to E. coli. ALF153, the most stable complex in the whole set, was essentially devoid of toxicity or ROS induction ability in all cells. These results suggest that CORMs have a relevant therapeutic potential as antimicrobial drugs since (i) they

  4. Comparative In vivo, Ex vivo, and In vitro Toxicity Studies of Engineered Nanomaterials

    Science.gov (United States)

    Efforts to reduce the number of animals in engineered nanomaterials (ENM) toxicity testing have resulted in the development of numerous alternative toxicity testing methods, but in vivo and in vitro results are still evolving and variable. This inconsistency could be due to the f...

  5. Toxicity testing in the 21 century: defining new risk assessment approaches based on perturbation of intracellular toxicity pathways.

    Directory of Open Access Journals (Sweden)

    Sudin Bhattacharya

    Full Text Available The approaches to quantitatively assessing the health risks of chemical exposure have not changed appreciably in the past 50 to 80 years, the focus remaining on high-dose studies that measure adverse outcomes in homogeneous animal populations. This expensive, low-throughput approach relies on conservative extrapolations to relate animal studies to much lower-dose human exposures and is of questionable relevance to predicting risks to humans at their typical low exposures. It makes little use of a mechanistic understanding of the mode of action by which chemicals perturb biological processes in human cells and tissues. An alternative vision, proposed by the U.S. National Research Council (NRC report Toxicity Testing in the 21(st Century: A Vision and a Strategy, called for moving away from traditional high-dose animal studies to an approach based on perturbation of cellular responses using well-designed in vitro assays. Central to this vision are (a "toxicity pathways" (the innate cellular pathways that may be perturbed by chemicals and (b the determination of chemical concentration ranges where those perturbations are likely to be excessive, thereby leading to adverse health effects if present for a prolonged duration in an intact organism. In this paper we briefly review the original NRC report and responses to that report over the past 3 years, and discuss how the change in testing might be achieved in the U.S. and in the European Union (EU. EU initiatives in developing alternatives to animal testing of cosmetic ingredients have run very much in parallel with the NRC report. Moving from current practice to the NRC vision would require using prototype toxicity pathways to develop case studies showing the new vision in action. In this vein, we also discuss how the proposed strategy for toxicity testing might be applied to the toxicity pathways associated with DNA damage and repair.

  6. Oral toxicity study of certain plant extracts containing pyrrolizidine alkaloids.

    Science.gov (United States)

    Şeremet, Oana Cristina; Bărbuceanu, Florica; Ionică, Floriana Elvira; Margină, Denisa Marilena; GuŢu, Claudia Maria; Olaru, Octavian Tudorel; Ilie, Mihaela; Gonciar, Veaceslav; Negreş, Simona; ChiriŢă, Cornel

    2016-01-01

    Pyrrolizidine alkaloids (PAs) are a class of toxic compounds which are found in plants. Poisoning caused by these toxins is associated with acute and chronic liver damage. Tussilago farfara (coltsfoot), Petasites hybridus (common butterbur), Senecio vernalis (eastern groundsel) and Symphytum officinale (comfrey) are traditional phytotherapic species, which beside the therapeutic bioactive compounds contain PAs. The aim of the paper was to assess the safety of some dry extracts obtained from these species. For the determination of acute toxicity, Organization for Economic Cooperation and Development (OECD) Guideline No. 423 was used. For the determination of repeated dose oral toxicity, Senecionis vernalis herba and Symphyti radix extracts (250 mg÷kg) were administrated, by gavage, for 28 days, and their effects on animal weight, liver and biliary functions, hepatic tissue and oxidative stress were investigated. After the acute toxicity testing, the dry extracts were placed in the GHS Category V (LD50>5000 mg÷kg, p.o.). For the subacute toxicity testing, no death or any signs of toxicity were observed. Also, no significant differences in biochemical parameters were observed between control and treated groups. The observed histopathological lesions were non-specific and were not consistent with the data reported in the literature for PAs exposure. In conclusion, the administration for 28 days, of the tested extracts, in a dose which correspond to a PAs concentration over the limits imposed in some countries, produced no hepatic and biliary toxic effects. Further studies, extended over a longer period of time, are needed in order to determine the safety of plant extracts containing PAs.

  7. Acute toxicity and the 28-day repeated dose study of a Siddha medicine Nuna Kadugu in rats

    Directory of Open Access Journals (Sweden)

    Ramaswamy Ramaswamy

    2012-10-01

    Full Text Available Abstract Background Nuna Kadugu (NK, a Siddha medicine prepared from leaves and fruits of Morinda Pubescens, used for the treatment of various skin diseases. Though NK has been widely used for several decades, no scientific report was available on its safety. Present study was undertaken to demonstrate the oral toxicity of NK in Sprague Dawley rats. Methods Acute and 28-day repeated oral toxicity studies were performed following OECD test guidelines 423 and 407, respectively, with minor modifications. In acute oral toxicity study, NK was administered at 2000mg/kg b.wt., p.o and animals were observed for toxic signs at 0, 0.5, 1, 4, 24 h and for next 14 days. Gross pathology was performed at the end of the study. In repeated dose, the 28- day oral toxicity study, NK was administered at 300, 600 and 900 mg/kg b.wt./p.o/day. Two satellite groups (control and high dose were also maintained to determine the delayed onset toxicity of NK. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In acute toxicity study, no treatment related death or toxic signs were observed with NK administration. In the repeated dose study, no significant differences in body weight changes, food / water intake, haematology, clinical biochemistry and electrolytes content were observed between control and NK groups. No gross pathological findings and difference in relative organ weights were observed between control and NK treated rats. Histopathological examination revealed no abnormalities with NK treatment. Conclusion Acute study reveals that the LD50 of NK is greater than 2000mg/kg, b.wt. in fasted female rats and can be classified as Category 5. 28-day repeated oral toxicity demonstrates that the No Observed Adverse Effect Level of NK is greater than 900 mg/kg b.wt./day, p.o in rats

  8. Implications of Animal Welfare on Toxicity Testing

    DEFF Research Database (Denmark)

    Meyer, Otto A.

    1993-01-01

    The testing strategy for chemical substances is discussed with regard to obtaining improved quality of data for health assessment while respecting the ethical responsibility for consideration of the welfare of the animals involved. Ensuring animal welfare without indulging too much in anthropomor......The testing strategy for chemical substances is discussed with regard to obtaining improved quality of data for health assessment while respecting the ethical responsibility for consideration of the welfare of the animals involved. Ensuring animal welfare without indulging too much...

  9. Single dose toxicity and biodistribution studies of [18F] fluorocholine

    International Nuclear Information System (INIS)

    Campos, Danielle C.; Santos, Priscilla F.; Silveira, Marina B.; Ferreira, Soraya Z.; Malamut, Carlos; Silva, Juliana B. da; Souza, Cristina M.; Campos, Liliane C.; Ferreira, Enio; Araujo, Marina R.; Cassali, Geovanni D.

    2013-01-01

    [ 18 F]Fluorocholine ( 18 FCH) is a valuable tool for non-invasive diagnosis using positron emission tomography (PET). This radiotracer has been proven to be highly effective in detecting recurrences and staging prostate cancer, diagnoses brain, breast, and esophageal tumors and also hepatocellular carcinoma. The higher uptake of fluorocholine by malignant tumors results from increased choline kinase activity due to accelerated cell multiplication and membrane formation. According to the Brazilian Health Surveillance Agency (ANVISA), radiopharmaceuticals have to be registered before commercialization. The aim of this work was to evaluate single dose toxicity and biodistribution of 18 FCH in mice, since preclinical safety studies are required for register. Experimental procedures were approved by the Ethics Committee on Animal Use (CEUA-IPEN/SP). Single dose toxicity and biodistribution studies were conducted in Swiss mice. No signs of toxicity were observed during clinical trial. No changes in the parameters which were examined, such as: body weight, food consumption, clinical pathology parameters or lesions microscopic were noted. Biodistribution results indicated high physiological tracer uptake in kidney, liver and heart 30 min after injection. Lower activities were recorded in other organs/tissues: pancreas, intestine, spleen, bone, bladder, muscle, brain and blood. Initial preclinical investigations showed no toxic effects of 18 FCH at investigated doses and a biodistribution profile very similar to other reports in literature. This information is essential to support future human trials. (author)

  10. Developmental toxicity study of D-tagatose in rats.

    Science.gov (United States)

    Kruger, C L; Whittaker, M H; Frankos, V H; Schroeder, R E

    1999-04-01

    D-tagatose is a low-calorie sweetener that tastes like sucrose. The developmental toxicity of D-tagatose was investigated in Crl:CD(SD)BR rats administered D-tagatose at three dose levels (4000, 12,000, and 20,000 mg/kg body wt/day) via gastric intubation on days 6-15 of gestation. No compound-related toxicity was seen among any of the maternal groups. No treatment-related clinical effects were seen in the maternal animals at the 4000 mg/kg/day dose level. At the mid- and high-dose levels, most maternal animals had unformed or watery stools; this effect was most prominent early in the treatment period (Gestation Days 6-8). This effect was attributed to the osmotic effect of the large amount of D-tagatose given to the animals at these doses. Since D-tagatose is not digested or absorbed to a large extent, most of the sugar passes into the colon where it absorbs water and is fermented by colonic bacteria. Mean weight gain for the low- and mid-dose animals was comparable to the control; however, the high-dose group experienced a mean weight loss over the Gestation Day 6-9 interval. Over the entire treatment interval, however, mean weight gain for the high-dose animals was comparable to control. The decreased weight gain in the high-dose animals during the Gestation Day 6-9 interval was considered to be a direct result of laxation. In addition to the effect of laxation on body weight, reduced food consumption also contributed to the decreased weight gain. In the low-dose animals, no effect on food consumption was seen; however, both mid- and high-dose animals had food consumption values that were statistically significantly lower than the control. Food consumption was lowest during the Gestation Day 6-9 interval, the period when laxation was most prominent. Food consumption rebounded and was statistically significantly higher than the control for the mid- and high-dose animals during the posttreatment interval. Maternal liver weight for the low-dose animals was

  11. Fluorosis in humans and animals

    Directory of Open Access Journals (Sweden)

    Mirona Palczewska-Komsa

    2015-12-01

    Full Text Available Fluorine compounds occur quite commonly in nature. They are exist in water, in soil, in geological decks, in living organisms. On human and animal bodies can influence moderately preferably or more often unfavorably. The deficiency or excess of this element results in undesirable effects in hard tissue, nervous tissue and other organs. Due to adverse effect of this element to a living organism it comes to fluorosis. The aim of the study was to determine the influence of the toxic effect of fluoride compounds on the human and other vertebrate animals depending on the time and dosage F- and the type of tissue and / or organ on the basis of the scientific literature. On the basis of the available publications, it was revealed that F- toxicity substantially depends on time and dose exposure on these element. Chronic fluorosis, more often than acute is observed in human and animals. Biological factors (including species differences susceptibility, metabolic activity of tissue and environmental factors can accumulate, which increases probability of F- toxicity for living organisms.

  12. A big data approach to the concordance of the toxicity of pharmaceuticals in animals and humans.

    Science.gov (United States)

    Clark, Matthew; Steger-Hartmann, Thomas

    2018-07-01

    Although lack of efficacy is an important cause of late stage attrition in drug development the shortcomings in the translation of toxicities observed during the preclinical development to observations in clinical trials or post-approval is an ongoing topic of research. The concordance between preclinical and clinical safety observations has been analyzed only on relatively small data sets, mostly over short time periods of drug approvals. We therefore explored the feasibility of a big-data analysis on a set of 3,290 approved drugs and formulations for which 1,637,449 adverse events were reported for both humans animal species in regulatory submissions over a period of more than 70 years. The events reported in five species - rat, dog, mouse, rabbit, and cynomolgus monkey - were treated as diagnostic tests for human events and the diagnostic power was computed for each event/species pair using likelihood ratios. The animal-human translation of many key observations is confirmed as being predictive, such as QT prolongation and arrhythmias in dog. Our study confirmed the general predictivity of animal safety observations for humans, but also identified issues of such automated analyses which are on the one hand related to data curation and controlled vocabularies, on the other hand to methodological changes over the course of time. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. In vivo assessment of toxicity and pharmacokinetics of methylglyoxal

    International Nuclear Information System (INIS)

    Ghosh, Manju; Talukdar, Dipa; Ghosh, Swapna; Bhattacharyya, Nivedita; Ray, Manju; Ray, Subhankar

    2006-01-01

    Previous in vivo studies from several laboratories had shown remarkable curative effect of methylglyoxal on cancer-bearing animals. In contrast, most of the recent in vitro studies have assigned a toxic role for methylglyoxal. The present study was initiated with the objective to resolve whether methylglyoxal is truly toxic in vivo and to reassess its therapeutic potential. Four species of animals, both rodent and non-rodent, were treated with different doses of methylglyoxal through oral, subcutaneous and intravenous routes. Acute (treatment for only 1 day) toxicity tests had been done with mouse and rat. These animals received 2, 1 and 0.3 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Chronic (treatment for around a month) toxicity test had been done with mouse, rat, rabbit and dog. Mouse, rat and dog received 1, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Rabbit received 0.55, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. It had been observed that methylglyoxal had no deleterious effect on the physical and behavioral pattern of the treated animals. Fertility and teratogenecity studies were done with rats that were subjected to chronic toxicity tests. It had been observed that these animals produced healthy litters indicating no damage of the reproductive systems as well as no deleterious effect on the offspring. Studies on several biochemical and hematological parameters of methylglyoxal-treated rats and dogs and histological studies of several organs of methylglyoxal-treated mouse were performed. These studies indicated that methylglyoxal had no apparent deleterious effect on some vital organs of these animals. A detailed pharmacokinetic study was done with mouse after oral administration of methylglyoxal. The effect of methylglyoxal alone and in

  14. Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models.

    Science.gov (United States)

    Plengsuriyakarn, Tullayakorn; Viyanant, Vithoon; Eursitthichai, Veerachai; Picha, Porntipa; Kupradinun, Piengchai; Itharat, Arunporn; Na-Bangchang, Kesara

    2012-03-27

    Chemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed. The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR), the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO) and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL), fruits of Piper chaba Hunt. (De-Plee: PC), and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF) were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA) was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification. Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight) as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively). PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL), analgesic (CUR and PPF), antipyretic (CUR and AL), antihypertensive (ZO

  15. The Effect of Toxic Cyanobacteria on Human and Animal Health

    Science.gov (United States)

    The study of environmental health typically focuses on human populations. However, companion animals, livestock and wildlife also experience adverse health effects from environmental pollutants. Animals may experience direct exposure to pollutants unlike people in most ambient ex...

  16. On the impact of second generation mating and offspring in multi-generation reproductive toxicity studies on classification and labelling of substances in Europe

    DEFF Research Database (Denmark)

    Rorije, Emiel; Muller, André; Beekhuijzen, Manon E.W.

    2011-01-01

    The possible impact on classification and labelling decisions of effects observed in second generation parental (P1) and offspring (F2) parameters in multi-generation studies was investigated. This was done for 50 substances classified as reproductive toxicants in Europe, for which a multi-genera...... and reduced animal use, provide strong further support for replacement of the classical two-generation reproductive toxicity study by the EOGRTS in regulatory reproductive toxicity assessment....

  17. Histidine protects against zinc and nickel toxicity in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    John T Murphy

    2011-03-01

    Full Text Available Zinc is an essential trace element involved in a wide range of biological processes and human diseases. Zinc excess is deleterious, and animals require mechanisms to protect against zinc toxicity. To identify genes that modulate zinc tolerance, we performed a forward genetic screen for Caenorhabditis elegans mutants that were resistant to zinc toxicity. Here we demonstrate that mutations of the C. elegans histidine ammonia lyase (haly-1 gene promote zinc tolerance. C. elegans haly-1 encodes a protein that is homologous to vertebrate HAL, an enzyme that converts histidine to urocanic acid. haly-1 mutant animals displayed elevated levels of histidine, indicating that C. elegans HALY-1 protein is an enzyme involved in histidine catabolism. These results suggest the model that elevated histidine chelates zinc and thereby reduces zinc toxicity. Supporting this hypothesis, we demonstrated that dietary histidine promotes zinc tolerance. Nickel is another metal that binds histidine with high affinity. We demonstrated that haly-1 mutant animals are resistant to nickel toxicity and dietary histidine promotes nickel tolerance in wild-type animals. These studies identify a novel role for haly-1 and histidine in zinc metabolism and may be relevant for other animals.

  18. Effects of protein-calorie malnutrition and refeeding on fluorouracil toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Gamelli, R.L.; Foster, R.S. Jr.

    1983-10-01

    Mice were used to study the effects of protein-calorie malnutrition and its reversal on granulocyte-macrophage production and fluorouracil's toxic effect on bone marrow. An in vitro quantitative clonal culture technique for bone marrow granulocyte-macrophage progenitor cells (GM-CFC) was used. Animals on a protein-free but otherwise complete diet for ten days had a significant contraction in total marrow cellularity and GM-CFC numbers paralleling the animal's weight loss. The acute toxic effect of fluorouracil on bone marrow was not increased in protein-deprived animals. On refeeding, there was a biphasic response in the degree of toxic effect on marrow. Animals refed for one day had significantly increased fluorouracil-related marrow abnormalities. However, animals refed for four days, when marrows were repleted, were partially protected from the drug's cytotoxic effects. The increased sensitivity in mice refed for one day was related to more GM-CFC in active DNA synthesis.

  19. Repeated sub-chronic oral toxicity study of xylooligosaccharides (XOS) in dogs.

    Science.gov (United States)

    Gao, Yonglin; Wang, Yunzhi; Li, Yanshen; Han, Rui; Li, Chunmei; Xiao, Lin; Cho, Susan; Ma, Yukui; Fang, Chao; Lee, Albert W

    2017-06-01

    In this study, Beagle dogs were administered xylooligosaccharide (XOS, CAS # 87099-0) at doses of 0, 1250, 2500, and 5000 mg/kg/day by oral gavage for 26 weeks. A 4-week recovery period was added to observe delayed or reversible toxicity. Measurements included body weight, food consumption, clinical observations, temperature, electrocardiogram (ECG), urinalysis, blood chemistry, hematology, organ weight, gross necropsy, and histopathological examination. Except for transient diarrhea or vomiting, no treatment-related adverse effects were noted. In the mid-dose groups, transitional diarrhea was observed in the initial 1-2 weeks. In the high-dose groups, diarrhea and/or vomiting were observed episodically over the duration of treatment. However, they disappeared after XOS was withdrawn in the recovery period. Although there was a tendency toward less weight gain in the high-dose group animal group, this is typical in animals and humans fed non-digestible carbohydrates. This chronic toxicity study demonstrated that the no observed adverse effect level (NOAEL) of XOS is 2500 mg/kg body weight (BW)/day. Based on body surface area (conversion factor of 0.54 for dogs to human), this corresponds to daily doses of 1350 mg/kg BW or 81-108 g XOS in human adults weighing 60-80 kg. Copyright © 2017. Published by Elsevier Inc.

  20. Exploratory study using proton induced X-ray emission analysis and histopathological techniques to determine the toxic burden of environmental pollutants

    International Nuclear Information System (INIS)

    Ejaz, Sohail; Ashraf, Muhammad; Shakir, Lubna; Ahmad, Nisar

    2012-01-01

    The aim of this novel research was to determine the toxic burden of increased elements in water resources on the inhabitant wild animals (squirrels, turtles, bats), using particle induced x-ray emission (PIXE) and histopathological approaches. PIXE analysis of skin, muscle, lung, liver and kidney revealed significant increase in Al, Cl, Fe, Mg, Mn, Si and V. Moreover, data clearly reflect a significant (P < 0.001) deposition of toxic elements (Al, Cl, Fe and K) in the lung producing interstitial/proliferative pneumonitis, intra-alveolar hemorrhages, and thickening of alveolar capillary walls. The results obtained from the liver samples emphasized that majority of the animals were intoxicated with Cl, Mg, S, Si and V, which have produced profound deterioration and swelling of the hepatocytes. Likewise, histopathology of the kidney sections spotlighted severe nephritis and degenerative changes, which could be associated with the elevated amount of Al, Cl and Mg. This data undoubtedly provide relevant information on the heavy burden of toxic elements and their pathological outcomes in wild animals and highlight their potential risks for human exposure. Thus, the information provided is critical for developing effective strategies in dealing with health hazards associated with elemental exposures. Highlights: ► The aim of this study was to determine environmental burden on wild animals. ► Elemental load was determined by PIXE and histological techniques. ► Lungs and liver were most affected organs. ► Environmental pollution is the main cause of different degenerative changes. - Toxic burden of environmental pollutants on wild animals

  1. Two new rodent models for actinide toxicity studies

    International Nuclear Information System (INIS)

    Taylor, G.N.; Jones, C.W.; Gardner, P.A.; Lloyd, R.D.; Mays, C.W.; Charrier, K.E.

    1981-01-01

    Two small rodent species, the grasshopper mouse (Onychomys leucogaster) and the deer mouse (Peromyscus maniculatus), have tenacious and high retention in the liver and skeleton of plutonium and americium following intraperitoneal injection of Pu and Am in citrate solution. Liver retention of Pu and Am in the grasshopper mouse is higher than liver retention in the deer mouse. Both of these rodents are relatively long-lived, breed well in captivity, and adapt suitably to laboratory conditions. It is suggested that these two species of mice, in which plutonium retention is high and prolonged in both the skeleton and liver, as it is in man, may be useful animal models for actinide toxicity studies

  2. [Toxicity studies of landiolol hydrochloride (ONO-1101) (2). 4-week repeated dose intravenous toxicity study in rats with 4-week recovery test].

    Science.gov (United States)

    Yamaguchi, K; Yanagi, H; Shimizu, K; Sakai, M; Nishibata, K; Oida, H; Shinomiya, K; Suzuki, Y; Yonezawa, H; Fujita, T

    1997-12-01

    4-week repeated dose toxicity study with 4-week recovery test of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in Sprague-Dawley (SD) rats. ONO-1101 was administered intravenously to rats of both sexes at a dose level of 0 (control), 12.5, 25, 50 or 100 mg/kg/day. In the 100 mg/kg/day group, bradypnea or dyspnea was seen in all animals, pale in ear, eye and foot, tremor, reddish lacrimation and loss of righting reflex were also observed in some animals right after administration, and then those signs disappeared within 1 min after administration. During the treatment period, 3/20 animals of each sex in the 100 mg/kg/day showed clonic convulsion and died within 2 min after administration. No clinical changes were seen in the 50 mg/kg/day group or lower. Histopathological findings showed atrophy of the submaxillary gland in females and vessel-wall thickening and perivascular fibrosis of the injection site (tail) in both sexes at 100 mg/kg/day, however those changes were reversible. ONO-1101 did not effect on body weight, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weights or necropsy at any doses. These results indicate that the no-adverse-effect level of ONO-1101 in rats is 50 mg/kg/day for both sexes in this study.

  3. Systemic toxicity of ropivacaine during ovine pregnancy.

    Science.gov (United States)

    Santos, A C; Arthur, G R; Pedersen, H; Morishima, H O; Finster, M; Covino, B G

    1991-07-01

    Ropivacaine is a new amide local anesthetic structurally related to bupivacaine and mepivacaine. Its potency and duration of action are similar to those of bupivacaine but its therapeutic index may be greater. Since pregnancy enhances the cardiotoxicity of bupivacaine, the current study was devised to compare the toxicity of ropivacaine in chronically instrumented nonpregnant and pregnant ewes during continuous intravenous infusion of the drug at the rate of 0.5 mg.kg-1.min-1. In all animals, symptoms of local anesthetic toxicity occurred in the usual order--convulsions, hypotension, apnea, and circulatory collapse. There were no significant differences between the two groups of animals in the doses and plasma concentrations of ropivacaine associated with each toxic manifestations. For example, circulatory collapse occurred at a mean dose of 11.3 +/- 1.1 mg.kg-1 in nonpregnant and 12.4 +/- 0.9 mg.kg-1 in pregnant animals, with corresponding plasma concentrations of 7.3 +/- 0.3 and 9.6 +/- 2.1 micrograms.ml-1 (P = not significant). Protein binding of ropivacaine in the concentration range associated with toxic manifestations was similar in sera obtained from nonpregnant and pregnant ewes. In conclusion, ovine pregnancy does not enhance the systemic toxicity of ropivacaine, possibly because of an absence of gestation-related increase in the availability of free drug.

  4. Drug induced acute kidney injury: an experimental animal study

    International Nuclear Information System (INIS)

    Khan, M.W.A.; Khan, B.T.; Qazi, R.A.; Ashraf, M.; Waqar, M.

    2017-01-01

    Objective: To assess the extent of drug induced nephrotoxicity in laboratory animals for determining the role and extent of iatrogenic kidney damage in patients exposed to nephrotoxic drugs in various clinical setups. Study Design: Randomized control trail. Place and Duration of study: Pharmacology department and animal house of Army Medical College from Jan 2011 to Aug 2011. Material and Methods: Thirty six mixed breed rabbits were used in this study. Animals were randomly divided into six groups consisting of six rabbits in each. Groups were named A, B, C, D, E and F. Group A was control group. Group B was given 0.9% normal saline. Group C rabbits were given acute nephrotoxic single dose of amphotericin B deoxycholate. Group D received 0.9% normal saline 10ml/kg followed by amphotericin B infusion. Group E was injected acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Group F received saline loading along with acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Results: Biochemical and histopathological analysis showed significant kidney injury in rabbits exposed to acute nephrotoxic doses of amphotericin B and cyclosporine. Toxicity was additive when the two drugs were administered simultaneously. Group of rabbits with saline loading had significantly lesser kidney damage. Conclusion: Iatrogenic acute kidney damage is a major cause of morbidity in experimental animals exposed to such nephrotoxic drugs like amphotericin B and cyclosporine, used either alone or in combination. Clinical studies are recommended to assess the extent of iatrogenic renal damage in patients and its economic burden. Efficient and cost effective protective measure may be adopted in clinical setups against such adverse effects. (author)

  5. Study on the Potential Toxicity of a Thymoquinone-Rich Fraction Nanoemulsion in Sprague Dawley Tats

    Directory of Open Access Journals (Sweden)

    Maznah Ismail

    2013-06-01

    Full Text Available Toxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. A newly developed thymoquinone-rich fraction nanoemulsion (TQRFNE has been prepared using a high pressure homogenizer. The purpose of this study was to investigate the potential acute toxicity of this nanoemulsion in Sprague Dawley rats. The acute toxicity studies were conducted as per the OECD guidelines 425, allowing for the use of test dose limit of 20 mL TQRFNE (containing 44.5 mg TQ/kg. TQRFNE and distilled water (DW as a control were administered orally to both sexes of rats on Day 0 and observed for 14 days. All the animals appeared normal, and healthy throughout the study. There was no observed mortality or any signs of toxicity during the experimental period. The effects of the TQRFNE and DW groups on general behavior, body weight, food and water consumption, relative organ weight, hematology, histopathology, and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control (DW group. The administration of 20 mL TQRFNE /kg was not toxic after an acute exposure.

  6. Single dose toxicity and biodistribution studies of [{sup 18}F] fluorocholine

    Energy Technology Data Exchange (ETDEWEB)

    Campos, Danielle C.; Santos, Priscilla F., E-mail: dcc@cdtn.br [Universidade Federal de Minas Gereais (INCT-MM/UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina. Instituto Nacional de Ciencia e Tecnologia de Medicina Molecular; Silveira, Marina B.; Ferreira, Soraya Z.; Malamut, Carlos; Silva, Juliana B. da, E-mail: radiofarmacoscdtn@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Producao de Radiofarmacos; Souza, Cristina M.; Campos, Liliane C.; Ferreira, Enio; Araujo, Marina R.; Cassali, Geovanni D., E-mail: cassalig@icb.ufmg.br [Universidade Federal de Minas Gerais (LPC/UFMG), Belo Horizonte, MG (Brazil). Lab. de Patologia Comparada

    2013-07-01

    [{sup 18}F]Fluorocholine ({sup 18}FCH) is a valuable tool for non-invasive diagnosis using positron emission tomography (PET). This radiotracer has been proven to be highly effective in detecting recurrences and staging prostate cancer, diagnoses brain, breast, and esophageal tumors and also hepatocellular carcinoma. The higher uptake of fluorocholine by malignant tumors results from increased choline kinase activity due to accelerated cell multiplication and membrane formation. According to the Brazilian Health Surveillance Agency (ANVISA), radiopharmaceuticals have to be registered before commercialization. The aim of this work was to evaluate single dose toxicity and biodistribution of {sup 18}FCH in mice, since preclinical safety studies are required for register. Experimental procedures were approved by the Ethics Committee on Animal Use (CEUA-IPEN/SP). Single dose toxicity and biodistribution studies were conducted in Swiss mice. No signs of toxicity were observed during clinical trial. No changes in the parameters which were examined, such as: body weight, food consumption, clinical pathology parameters or lesions microscopic were noted. Biodistribution results indicated high physiological tracer uptake in kidney, liver and heart 30 min after injection. Lower activities were recorded in other organs/tissues: pancreas, intestine, spleen, bone, bladder, muscle, brain and blood. Initial preclinical investigations showed no toxic effects of {sup 18}FCH at investigated doses and a biodistribution profile very similar to other reports in literature. This information is essential to support future human trials. (author)

  7. Toxicity study about a medicinal plant Casearia sylvestris: A contribution to the Brazilian Unified Health System (SUS).

    Science.gov (United States)

    Ameni, A Z; Latorre, O A; Torres, L M B; Górniak, S L

    2015-12-04

    Casearia sylvestris S.w (Salicaceae) is catalogued by the Brazilian Unified Health System as a plant of interest for the Brazilian population with the purpose of treating inflammatory disorders, such as pain and gastrointestinal disorders based on the folk use and some literature about efficacy; however, no toxicological studies concerned the safety of extract fluid of this plant have been reported. The present study was carried out to evaluate the acute and subchronic toxicity of the hydroethanolic extract fluid (FE) obtained from leaves of C. sylvestris in Wistar rats. In the acute toxicity test three female Wistar rats were treated with a single dose of FE (2000 mg/kg) administered by oral gavage and observed for 14 days in order to identify signs of toxicity or death. In subchronic toxicity study animals received, by daily gavage three doses 60, 120 and 240 mg/kg of the FE of the plant for 28 and 90 days. The animals were observed daily for clinical signs and mortality. Body weight and food consumption were measured weekly and at the end of treatment were analysed hematological, biochemical and histopathological parameters. Also was analysed the cellularity of bone marrow and spleen. Moreover, phytochemical analysis by HPLC-PDA-ESI(+)/MS and CG/MS/EI was carried out to qualify the constituents of the extract. The results of acute study indicated that the LD50 is higher than 2000 mg/kg and at 28 and 90 day oral toxicity showed that there were no toxic effects detected in any of the parameters evaluated: body weight and relative organ weight, general behavioral changes, haematological and biochemical parameters and histopathological examination. The analysis by HPLC-PDA-ESI(+)/MS and CG/MS/EI identified the flavonoids rutin, quercetin and luteolin and also chlorogenic on the extract. Based on this study the hydroethanolic fluid extract of C. sylvestris could be safe even when used over a long period for therapeutic uses proposed by the Brazilian Unified Health

  8. Effects of synthetic and natural toxicants on livestock.

    Science.gov (United States)

    Shull, L R; Cheeke, P R

    1983-07-01

    Synthetic and natural toxicants are constituents of soil, air, water and foodstuffs. Their impact on animal agriculture has resulted from acute and chronic intoxication and residues transferred into meat, dairy and poultry products. Recent advances in analytical chemistry and the sciences associated with toxicology have allowed better assessment of the hazard of toxicants on animals including man. Historically, natural toxicants (phytotoxins, mycotoxins and minerals) that are associated with many common feedstuffs accounted for toxicity episodes of epidemic proportions. Most synthetic chemicals (pesticides, nonpesticidal organic chemicals and drugs) have been introduced in increasing numbers since the 1940's. In the 1960's and '70's, recognition of the need to control their environmental distribution stimulated the introduction of numerous laws and regulations. In the last decade, several problematic synthetic chemicals have been banned, particularly those found to persist in the environment or those confirmed or suspected as carcinogens in humans. At the farm level, the development of various preventative management strategies has decreased the exposure of livestock to natural toxicants. In the future, the impact of natural toxicants on animal agriculture is expected to lessen as their existence, etiology and toxicology are determined. On the other hand, synthetic chemicals will continue to threaten animal health as greater numbers and quantities are released into the environment. These challenges should stimulate a greater involvement of animal scientists in toxicology.

  9. Safety assessment of non-animal chondroitin sulfate sodium: Subchronic study in rats, genotoxicity tests and human bioavailability.

    Science.gov (United States)

    Miraglia, Niccolò; Bianchi, Davide; Trentin, Antonella; Volpi, Nicola; Soni, Madhu G

    2016-07-01

    Chondroitin sulfate, an amino sugar polymer made of glucuronic acid and N-acetyl-galactosamine, is used in dietary supplements to promote joint health. Commonly used chondroitin sulfate is of animal origin and can pose potential safety problems including bovine spongiform encephalopathy (BSE). The objective of the present study was to investigate potential adverse effects, if any, of microbial derived chondroitin sulfate sodium (CSS) in subchronic toxicity, genotoxicity and bioavailability studies. In the toxicity study, Sprague Dawley rats (10/sex/group) were gavaged with CSS at dose levels of 0, 250, 500 and 1000 mg/kg body weight (bw)/day for 90-days. No mortality or significant changes in clinical signs, body weights, body weight gain or feed consumption were noted. Similarly, no toxicologically relevant treatment-related changes in hematological, clinical chemistry, urinalysis and organ weights were noted. Macroscopic and microscopic examinations did not reveal treatment-related abnormalities. In vitro mutagenic and clastogenic potentials as evaluated by Ames assay, chromosomal aberration test and micronucleus assay did not reveal genotoxicity of CSS. In pharmacokinetic study in human, CSS showed higher absorption as compared to chondroitin sulfate of animal origin. The results of subchronic toxicity study supports the no-observed-adverse-effect level (NOAEL) for CSS as 1000 mg/kg bw/day, the highest dose tested. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Systematic review of the effect of intravenous lipid emulsion therapy for local anesthetic toxicity

    DEFF Research Database (Denmark)

    Høgberg, Lotte Christine Groth; Bania, Theodore C; Lavergne, Valéry

    2016-01-01

    BACKGROUND: Following national and regional recommendations, intravenous lipid emulsion (ILE) has become established in clinical practice as a treatment for acute local anesthetic (LA) toxicity, although evidence of efficacy is limited to animal studies and human case reports. A collaborative lipid......-defined inclusion and exclusion criteria. Pre-treatment experiments, pharmacokinetic studies not involving toxicity and studies that did not address antidotal use of ILE were excluded. RESULTS: We included 113 studies and reports. Of these, 76 were human and 38 animal studies. One publication included both a human...... case report and an animal study. Human studies included one randomized controlled crossover trial involving 16 healthy volunteers. The subclinical LA toxicity design did not show a difference in the effects of ILE versus saline. There was one case series and 73 case reports of ILE use in the context...

  11. A strategy for systemic toxicity assessment based on non-animal approaches: The Cosmetics Europe Long Range Science Strategy programme.

    Science.gov (United States)

    Desprez, Bertrand; Dent, Matt; Keller, Detlef; Klaric, Martina; Ouédraogo, Gladys; Cubberley, Richard; Duplan, Hélène; Eilstein, Joan; Ellison, Corie; Grégoire, Sébastien; Hewitt, Nicola J; Jacques-Jamin, Carine; Lange, Daniela; Roe, Amy; Rothe, Helga; Blaauboer, Bas J; Schepky, Andreas; Mahony, Catherine

    2018-03-02

    When performing safety assessment of chemicals, the evaluation of their systemic toxicity based only on non-animal approaches is a challenging objective. The Safety Evaluation Ultimately Replacing Animal Test programme (SEURAT-1) addressed this question from 2011 to 2015 and showed that further research and development of adequate tools in toxicokinetic and toxicodynamic are required for performing non-animal safety assessments. It also showed how to implement tools like thresholds of toxicological concern (TTCs) and read-across in this context. This paper shows a tiered scientific workflow and how each tier addresses the four steps of the risk assessment paradigm. Cosmetics Europe established its Long Range Science Strategy (LRSS) programme, running from 2016 to 2020, based on the outcomes of SEURAT-1 to implement this workflow. Dedicated specific projects address each step of this workflow, which is introduced here. It tackles the question of evaluating the internal dose when systemic exposure happens. The applicability of the workflow will be shown through a series of case studies, which will be published separately. Even if the LRSS puts the emphasis on safety assessment of cosmetic relevant chemicals, it remains applicable to any type of chemical. Copyright © 2018. Published by Elsevier Ltd.

  12. The use of mice as animal model for testing acute toxicity (LD-50 of toxic shock syndrome toxin Utilização de camundongos como modelo animal para a verificação da toxicidade aguda da toxina-1 da síndrome do choque tóxico

    Directory of Open Access Journals (Sweden)

    R.S. Dias

    2009-02-01

    Full Text Available Acute toxicity test (LD-50 using toxic shock syndrome toxin (TSST-1 was tested in BALB/c, C57BL/6 and Swiss mice. Animals (n = 10 were intraperitoneally injected with TSST-1 (0.01-10.0µg/mouse followed 4h later by potentiating dose of lipopolysaccharide (75.0µg of LPS - E. coli O111:B4 and cumulative mortality was recorded over 72h. Control animals received either TSST-1 or LPS alone. The data were submitted to qui-Square test and acute toxicity test was calculated by probit analysis (confidence limits expressed as µg toxin/kg. BALB/c mice was the most sensitive (20.0µg/kg, 95% confidence limits: 9.0-92.0 followed by C57BL/6 (38.5µg/kg, 95% confidence limits: 9.11- 401.6. Data from Swiss mice was not conclusive, indicating only low sensitivity. Selection of the animal model and standardization of the experiment are fundamental for the development of serum neutralization tests used for final quality control of vaccine production.A toxicidade aguda (DL-50 da toxina da síndrome do choque tóxico (TSST-1 foi testada em linhagens de camundongos BALB/c, C57BL/6 e Suíça. Os animais (n=10 inoculados intraperitoneal com doses crescentes de toxina (0,01 - 10,0µg/animal receberam 4h após 75µg de LPS (E. coli O111: B4. A toxicidade aguda (DL50 foi observada por um período de 72h e os dados submetidos ao teste de qui- quadrado. Os resultados e os limites de confiança foram expressos em µg de toxina/kg. A linhagem BALB/c apresentou maior sensibilidade (20µg/kg - limite de confiança a 95% entre 9,0- 92,0, seguida da C57BL/6 (38,5µg/kg - limite de confiança a 95% entre 9,11 - 401,6. A amplitude dos limites de confiança deve-se à natureza da toxina, ao mecanismo de ação, a via de inoculação e ao animal utilizado. A seleção do modelo animal e a padronização do experimento são fundamentais para o desenvolvimento de testes de soro neutralização para fins de controle de qualidade do processo de produção de vacinas.

  13. [Glyphosate--a non-toxic pesticide?].

    Science.gov (United States)

    Pieniazek, Danuta; Bukowska, Bozena; Duda, Wirgiliusz

    2003-01-01

    Glyphosate is currently the most commonly applied herbicide and its use is still growing. Nowadays, over 50 commercial preparations containing this compound are used, and these formulations are much more toxic than their active compound, glyphosate, owing to the presence of many surfactants and carrier compounds. Toxicological investigations provide evidence that glyphosate is an extremely "safe" herbicide for animals. This is why its use in agriculture is universal. In June 1991, the Environmental Protection Agency (EPA) categorized this compound into class E (according to EPA there are five categories of carcinogenicity), which means that it is probably not carcinogenic to humans. Unfortunately, the study carried out by Swedish oncologists in 2001 showed that glyphosate may induce cancer of the lymphatic system. The results of the Swedish study have changed our opinion about "safety" of this herbicide. Investigations concerning both its accumulation and toxic effect in animals and plants are now under way in many laboratories.

  14. Acute toxicity and genotoxicity study of fermented traditional herb formula Guibi-tang.

    Science.gov (United States)

    Park, Hwayong; Hwang, Youn-Hwan; Yang, Hye Jin; Kim, Hyun-Kyu; Song, Kyung Seuk; Ma, Jin Yeul

    2014-10-28

    Guibi-tang (Guipi-tang in Chinese and Kihi-to in Japanese) is a multi-herb traditional medicine commonly prescribed to treat psychoneurosis in East Asia. Although this medicine has been widely used, there is little available information on the safety and toxicity of Guibi-tang, especially on the fermented one. Guibi-tang, composed of 12 herbs, was fermented with bacteria and lyophilized. Single dose acute toxicity in rats was observed for 14 days after administration. Genetic toxicity of fermented Guibi-tang was evaluated on bacterial reverse mutation in Salmonella and Escherichia spp., chromosome aberrations in Chinese hamster ovary cells, and micronucleus formation in mice. Ingredients in FGBT were identified and quantified by high performance liquid chromatography-mass spectrometry. In acute oral toxicity study, behavior, clinical signs and body weight changes were normal observing in all experimental animals. No revertant colonies were found in any bacterial cultures examined. Morphological or numerical anomalies and significant increased number of aberrant metaphases were not observed. Micronucleus assay showed no significant increases in the frequency of inducing micronuclei in any dose examined. Decursinol, decursin, glycyrrhizin, and 6-gingerol in fermented Guibi-tang were identified and quantitated. As a whole, no acute and genotoxic effects were found in all the assays and parameters analyzed. Fermented Guibi-tang was recognized as safe and non-toxic, and therefore can be used for applications of traditional medicine in modern complementary and alternative therapeutics and health care. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Toxicity of carbon nanotubes: A review.

    Science.gov (United States)

    Francis, Arul Prakash; Devasena, Thiyagarajan

    2018-03-01

    Carbon nanotubes (CNTs) are widely used in the aerospace, automotive, and electronics industries because of their stability, enhanced metallic, and electrical properties. CNTs are also being investigated for biomedical applications such as drug delivery systems and biosensors. However, the toxic potential of CNTs was reported in various cell lines and animal models. The toxicity depends on diverse properties of the CNTs, such as length, aspect ratio, surface area, degree of aggregation, purity, concentration, and dose. In addition, CNTs and/or associated contaminants were well known for oxidative stress, inflammation, apoptosis, pulmonary inflammation, fibrosis, and granuloma in lungs. The increased production of CNTs likely enhanced the possibility of its exposure in people. Studies on the toxicity of CNTs are mainly focused on the pulmonary effects after intratracheal administration, and only a few studies are reported about the toxicity of CNTs via other routes of exposure. So, it is essential to consider the chronic toxicity of CNTs before using them for various biomedical applications. This review focuses on the potential toxicities of CNTs.

  16. Prospects for new information relevant to radiation protection from studies of experimental animals

    International Nuclear Information System (INIS)

    McClellan, R.O.

    1988-01-01

    The theory underlying radiation protection was developed from studies of people, laboratory animals, tissues, cells and macromolecules. Data on people were obtained from opportunistic studies of individuals previously exposed to radiation. Rarely has it been possible to conduct prospective studies of people exposed to known quantities of radiation, which sharply restricts the nature of questions that they can address. In contrast, studies using laboratory animals and simpler biological systems can be designed to address specific questions, using controlled exposure conditions. In-vitro research with macromolecules, cells and tissues leads to understanding normal and disease processes in isolated biological components. Studies of the intact animals provide opportunities to study in vivo interactive mechanisms observed in vitro and their role in development of radiation-induced diseases such as cancer. In the future, studies of intact animals should prove increasingly valuable in linking new knowledge at the subanimal level with the more fragmentary information obtained from direct observations on people. This will provide insight into important issues such as (a) effects of low-level radiation exposures, (b) mechanism of cancer induction at high versus low radiation doses, and (c) influence of factors such as nutrition and exposure to chemicals on radiation-induced cancer. This presentation describes strategies for conducting and integrating results of research using macromolecules, cells, tissues, laboratory animals and people to improve our understanding of radiation-induced cancer. It will also emphasize the problems encountered in studies at all levels of biological organization when the disease is observed in low excess incidence long after exposure to the toxicant

  17. One Health and Toxic Cyanobacteria

    Science.gov (United States)

    One Health and toxic cyanobacteria Blooms of toxic freshwater blue-green algae or cyanobacteria (HABs) have been in the news after HABs associated with human and animal health problems have been reported in Florida, California and Utah during 2016. HABs occur in warm, slow moving...

  18. Neurological effects of white spirit: Contribution of animal studies during a 30-year period

    DEFF Research Database (Denmark)

    Nielsen, Gunnar Damgård; Lund, Søren Peter; Ladefoged, Ole

    2006-01-01

    Numerous studies have suggested that long-term occupational exposure to white spirit may cause chronic toxic encephalopathy (WHO 1996). This review summarizes the chronic nervous system effects of white spirit in animal studies during a 30-year period. First, routine histopathology was consistently...... unable to reveal adverse peripheral or central nervous system effects after inhalation of white spirit. Second, neurobehavioural studies in animals showed no adverse effect after inhalation of white spirit with a high content of aromatics in contrast to what was found with products with a low content....... Third, white spirit with a high content of aromatics induced adverse neurochemical changes at inhalation of 400 ppm and possibly already at 100 ppm. In the studied parameters, white spirit with a low content of aromatics showed no clear adverse neurochemical effects at inhalation of 400 ppm...

  19. Progress Toward Replacing Animals in Toxicity Testing for Cosmetics

    OpenAIRE

    Nye, Marisa B.

    2006-01-01

    In the 1980’s, animal rights activists successfully motivated the cosmetic industry to begin researching alternatives to animal tests. The European Union has taken action to stimulate development and validation of alternatives to animal testing through the Sixth and Seventh Amendments to the Cosmetics Directive. In this paper, I will briefly describe the history of the search for alternatives to animal testing for cosmetics. I will then discuss the progress that has been ma...

  20. Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition

    DEFF Research Database (Denmark)

    Sørli, Jorid Birkelund; Huang, Yishi; Da Silva, Emilie

    2018-01-01

    impregnation products using the constant flow through set-up of the constrained drop surfactometer to determine if they inhibited LS function or not. The same products were tested in a mouse inhalation bioassay to determine their toxicity in vivo. The sensitivity was 100%, i.e. the in vitro method predicted...... the chemical composition of the products and induction of toxicity. The currently accepted method for determination of acute inhalation toxicity is based on experiments on animals; it is time-consuming, expensive and causes stress for the animals. Impregnation products are present on the market in large...... numbers and amounts and exhibit great variety. Therefore, an alternative method to screen for acute inhalation toxicity is needed. The aim of our study was to determine if inhibition of lung surfactant by impregnation products in vitro could accurately predict toxicity in vivo in mice. We tested 21...

  1. Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Xie Shuyu

    2011-11-01

    Full Text Available Abstract Background Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN. Methods Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD50 was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters. Results After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group. Conclusions The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the

  2. Six-month low level chlorine dioxide gas inhalation toxicity study with two-week recovery period in rats

    Directory of Open Access Journals (Sweden)

    Akamatsu Akinori

    2012-02-01

    Full Text Available Abstract Background Chlorine dioxide (CD gas has a potent antimicrobial activity at extremely low concentration and may serve as a new tool for infection control occupationally as well as publicly. However, it remains unknown whether the chronic exposure of CD gas concentration effective against microbes is safe. Therefore, long-term, low concentration CD gas inhalation toxicity was studied in rats as a six-month continuous whole-body exposure followed by a two-week recovery period, so as to prove that the CD gas exposed up to 0.1 ppm (volume ratio is judged as safe on the basis of a battery of toxicological examinations. Methods CD gas at 0.05 ppm or 0.1 ppm for 24 hours/day and 7 days/week was exposed to rats for 6 months under an unrestrained condition with free access to chow and water in a chamber so as to simulate the ordinary lifestyle in human. The control animals were exposed to air only. During the study period, the body weight as well as the food and water consumptions were recorded. After the 6-month exposure and the 2-week recovery period, animals were sacrificed and a battery of toxicological examinations, including biochemistry, hematology, necropsy, organ weights and histopathology, were performed. Results Well regulated levels of CD gas were exposed throughout the chamber over the entire study period. No CD gas-related toxicity sign was observed during the whole study period. No significant difference was observed in body weight gain, food and water consumptions, and relative organ weight. In biochemistry and hematology examinations, changes did not appear to be related to CD gas toxicity. In necropsy and histopathology, no CD gas-related toxicity was observed even in expected target respiratory organs. Conclusions CD gas up to 0.1 ppm, exceeding the level effective against microbes, exposed to whole body in rats continuously for six months was not toxic, under a condition simulating the conventional lifestyle in human.

  3. Cyclosporine toxicity in immunosuppressed streptozotocin-diabetic nonhuman primates

    International Nuclear Information System (INIS)

    Wijkstrom, Martin; Kirchhof, Nicole; Graham, Melanie; Ingulli, Elizabeth; Colvin, Robert B.; Christians, Uwe; Hering, Bernhard J.; Schuurman, Henk-Jan

    2005-01-01

    Streptozotocin (STZ) is widely applied in animal models of insulin-dependent diabetes mellitus. Adverse effects of STZ mainly concern liver and kidney. In nonhuman primates a single 100-150 mg/kg dose invariably induces diabetes with only rare adverse effects. We report one animal with renal failure necessitating sacrifice. Body weight (age) might be a confounding factor, i.e. older animals might be more vulnerable to STZ-related toxicity. We therefore recommended to administer STZ on a mg/m 2 basis and not on a mg/kg basis. In our islet transplantation program nonhuman primates with STZ-induced diabetes received transplants under chronic immunosuppression including calcineurin inhibitors (cyclosporine, tacrolimus), drugs in the rapamycin class affecting growth factor-induced cell proliferation, and the sphingosine 1-phosphate receptor antagonist FTY720. Four animals developed renal failure and had to be sacrificed, most likely caused by cyclosporine. Kidney histology was typical for cyclosporine toxicity including thrombotic microangiopathy in glomeruli and fibrinoid necrosis of arteries, and for STZ toxicity including acute tubular necrosis and accumulations of erythroid precursors. This adverse effect was observed at a pharmacologically active cyclosporine exposure. Additionally, six diabetic animals without major adverse effects during cyclosporine or tacrolimus treatment are presented. We conclude that cyclosporine facilitates renal dysfunction in animals with STZ-induced diabetes, presumably related to an increased vulnerability to a toxic insult after STZ administration

  4. Disrupting self-assembly and toxicity of amyloidogenic protein oligomers by "molecular tweezers" - from the test tube to animal models.

    Science.gov (United States)

    Attar, Aida; Bitan, Gal

    2014-01-01

    Despite decades of research, therapy for diseases caused by abnormal protein folding and aggregation (amyloidoses) is limited to treatment of symptoms and provides only temporary and moderate relief to sufferers. The failure in developing successful disease-modifying drugs for amyloidoses stems from the nature of the targets for such drugs - primarily oligomers of amyloidogenic proteins, which are distinct from traditional targets, such as enzymes or receptors. The oligomers are metastable, do not have well-defined structures, and exist in dynamically changing mixtures. Therefore, inhibiting the formation and toxicity of these oligomers likely will require out-of-the-box thinking and novel strategies. We review here the development of a strategy based on targeting the combination of hydrophobic and electrostatic interactions that are key to the assembly and toxicity of amyloidogenic proteins using lysine (K)-specific "molecular tweezers" (MTs). Our discussion includes a survey of the literature demonstrating the important role of K residues in the assembly and toxicity of amyloidogenic proteins and the development of a lead MT derivative called CLR01, from an inhibitor of protein aggregation in vitro to a drug candidate showing effective amelioration of disease symptoms in animal models of Alzheimer's and Parkinson's diseases.

  5. Male-mediated developmental toxicity

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    Diana Anderson

    2014-02-01

    Full Text Available Male-mediated developmental toxicity has been of concern for many years. The public became aware of male-mediated developmental toxicity in the early 1990s when it was reported that men working at Sellafield might be causing leukemia in their children. Human and animal studies have contributed to our current understanding of male-mediated effects. Animal studies in the 1980s and 1990s suggested that genetic damage after radiation and chemical exposure might be transmitted to offspring. With the increasing understanding that there is histone retention and modification, protamine incorporation into the chromatin and DNA methylation in mature sperm and that spermatozoal RNA transcripts can play important roles in the epigenetic state of sperm, heritable studies began to be viewed differently. Recent reports using molecular approaches have demonstrated that DNA damage can be transmitted to babies from smoking fathers, and expanded simple tandem repeats minisatellite mutations were found in the germline of fathers who were exposed to radiation from the Chernobyl nuclear power plant disaster. In epidemiological studies, it is possible to clarify whether damage is transmitted to the sons after exposure of the fathers. Paternally transmitted damage to the offspring is now recognized as a complex issue with genetic as well as epigenetic components.

  6. In silico toxicology: computational methods for the prediction of chemical toxicity

    KAUST Repository

    Raies, Arwa B.; Bajic, Vladimir B.

    2016-01-01

    Determining the toxicity of chemicals is necessary to identify their harmful effects on humans, animals, plants, or the environment. It is also one of the main steps in drug design. Animal models have been used for a long time for toxicity testing. However, in vivo animal tests are constrained by time, ethical considerations, and financial burden. Therefore, computational methods for estimating the toxicity of chemicals are considered useful. In silico toxicology is one type of toxicity assessment that uses computational methods to analyze, simulate, visualize, or predict the toxicity of chemicals. In silico toxicology aims to complement existing toxicity tests to predict toxicity, prioritize chemicals, guide toxicity tests, and minimize late-stage failures in drugs design. There are various methods for generating models to predict toxicity endpoints. We provide a comprehensive overview, explain, and compare the strengths and weaknesses of the existing modeling methods and algorithms for toxicity prediction with a particular (but not exclusive) emphasis on computational tools that can implement these methods and refer to expert systems that deploy the prediction models. Finally, we briefly review a number of new research directions in in silico toxicology and provide recommendations for designing in silico models.

  7. In silico toxicology: computational methods for the prediction of chemical toxicity

    KAUST Repository

    Raies, Arwa B.

    2016-01-06

    Determining the toxicity of chemicals is necessary to identify their harmful effects on humans, animals, plants, or the environment. It is also one of the main steps in drug design. Animal models have been used for a long time for toxicity testing. However, in vivo animal tests are constrained by time, ethical considerations, and financial burden. Therefore, computational methods for estimating the toxicity of chemicals are considered useful. In silico toxicology is one type of toxicity assessment that uses computational methods to analyze, simulate, visualize, or predict the toxicity of chemicals. In silico toxicology aims to complement existing toxicity tests to predict toxicity, prioritize chemicals, guide toxicity tests, and minimize late-stage failures in drugs design. There are various methods for generating models to predict toxicity endpoints. We provide a comprehensive overview, explain, and compare the strengths and weaknesses of the existing modeling methods and algorithms for toxicity prediction with a particular (but not exclusive) emphasis on computational tools that can implement these methods and refer to expert systems that deploy the prediction models. Finally, we briefly review a number of new research directions in in silico toxicology and provide recommendations for designing in silico models.

  8. Biological reference materials and analysis of toxic elements

    Energy Technology Data Exchange (ETDEWEB)

    Subramanian, R; Sukumar, A

    1988-12-01

    Biological monitoring of toxic metal pollution in the environment requires quality control analysis with use of standard reference materials. A variety of biological tissues are increasingly used for analysis of element bioaccumulation, but the available Certified Reference Materials (CRMs) are insufficient. An attempt is made to review the studies made using biological reference materials for animal and human tissues. The need to have inter-laboratory studies and CRM in the field of biological monitoring of toxic metals is also discussed.

  9. A review of acrylamide toxicity and its mechanism

    Directory of Open Access Journals (Sweden)

    Ehsan Zamani

    2017-05-01

    Full Text Available Acrylamide (AA is an important industrial chemical agent that is mainly used in the production of polymers and copolymers. Recently it has been attention because of its production in the diet at high-temperature (>120 ºC processes such as cooking, frying, toasting, roasting or baking of high carbohydrate foods. According to high exposure to acrylamide, recognition of its toxic effect is necessary. Neurotoxicity, reproductive toxicity and immunotoxicity of AA were observed in several studies. There isn’t a clear mechanism that justifies this toxicity. In this study we reviewed the mechanisms of AA toxicity especially oxidative stress and apoptosis. AA can cause neurotoxicity, reproductive toxicity and genotoxicity on animal models. It showed neurotoxicity in human. We suggested the oxidative stress is the main factor for inducing of acrylamide toxicities. We advised that modifying of food processing methods can be as a good way for decreasing of AA production in foods.

  10. Exploring the Impact of Toxic Attitudes and a Toxic Environment on the Veterinary Healthcare Team.

    Science.gov (United States)

    Moore, Irene C; Coe, Jason B; Adams, Cindy L; Conlon, Peter D; Sargeant, Jan M

    2015-01-01

    The objective of this qualitative study was to compare veterinarians' and Registered Veterinary Technicians' (RVT's) perceptions of the veterinary healthcare team with respect to the impact of toxic attitudes and a toxic environment. Focus group interviews using a semi-structured interview guide and follow up probes were held with four veterinarian groups (23 companion animal veterinarians) and four Registered Veterinary Technician groups (26 RVTs). Thematic analysis of the discussions indicated both veterinarian and RVT participants felt team members with manifestations of toxic attitudes negatively impacted veterinary team function. These manifestations included people being disrespectful, being resistant to change, always wanting to be the "go to person," avoiding conflict, and lacking motivation. When conflict was ignored, or when people with toxic attitudes were not addressed, a toxic environment often resulted. A toxic environment sometimes manifested when "broken communication and tension between staff members" occurred as a result of employees lacking confidence, skills, or knowledge not being managed properly. It also occurred when employees did not feel appreciated, when there was difficulty coping with turnover, and when there were conflicting demands. The presence of people manifesting a toxic attitude was a source of frustration for both veterinarian and RVT participants. Prompt and consistent attention to negative behaviors is recommended to reduce the development of a toxic environment.

  11. Clopidogrel in a combined therapy with anticancer drugs-effect on tumor growth, metastasis, and treatment toxicity: Studies in animal models.

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    Agnieszka Denslow

    Full Text Available Clopidogrel, a thienopyridine derivative with antiplatelet activity, is widely prescribed for patients with cardiovascular diseases. In addition to antiplatelet activity, antiplatelet agents possess anticancer and antimetastatic properties. Contrary to this, results of some studies have suggested that the use of clopidogrel and other thienopyridines accelerates the progression of breast, colorectal, and prostate cancer. Therefore, in this study, we aimed to evaluate the efficacy of clopidogrel and various anticancer agents as a combined treatment using mouse models of breast, colorectal, and prostate cancer. Metastatic dissemination, selected parameters of platelet morphology and biochemistry, as well as angiogenesis were assessed. In addition, body weight, blood morphology, and biochemistry were evaluated to test toxicity of the studied compounds. According to the results, clopidogrel increased antitumor and/or antimetastatic activity of chemotherapeutics such as 5-fluorouracil, cyclophosphamide, and mitoxantrone, whereas it decreased the anticancer activity of doxorubicin, cisplatin, and tamoxifen. The mechanisms of such divergent activities may be based on the modulation of tumor vasculature via factors, such as transforming growth factor β1 released from platelets. Moreover, clopidogrel increased the toxicity of docetaxel and protected against mitoxantrone-induced toxicity, which may be due to the modulation of hepatic enzymes and protection of the vasculature, respectively. These results demonstrate that antiplatelet agents can be useful but also dangerous in anticancer treatment and therefore use of thienopyridines in patients undergoing chemotherapy should be carefully evaluated.

  12. Carbonyl emission and toxicity profile of diesel blends with an animal-fat biodiesel and a tire pyrolysis liquid fuel.

    Science.gov (United States)

    Ballesteros, R; Guillén-Flores, J; Martínez, J D

    2014-02-01

    In this paper, two diesel fuels, an animal-fat biodiesel and two diesel blends with the animal-fat biodiesel (50vol.%) and with a tire pyrolysis liquid (TPL) fuel (5vol.%) have been tested in a 4-cylinder, 4-stroke, turbocharged, intercooled, 2.0L Nissan diesel automotive engine (model M1D) with common-rail injection system and diesel oxidation catalyst (DOC). Carbonyl emissions have been analyzed both before and after DOC and specific reactivity of carbonyl profile has been calculated. Carbonyl sampling was carried out by means of a heated line, trapping the gas in 2,4-DNPH cartridges. The eluted content was then analyzed in an HPLC system, with UV-VIS detection. Results showed, on the one hand, an increase in carbonyl emissions with the biodiesel fraction in the fuel. On the other hand, the addition of TPL to diesel also increased carbonyl emissions. These trends were occasionally different if the emissions were studied after the DOC, as it seems to be selectivity during the oxidation process. The specific reactivity was also studied, finding a decrease with the oxygen content within the fuel molecule, although the equivalent ozone emissions slightly increased with the oxygen content. Finally, the emissions toxicity was also studied, comparing them to different parameters defined by different organizations. Depending on the point of study, emissions were above or below the established limits, although acrolein exceeded them as it has the least permissive values. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Predictive Model of Systemic Toxicity (SOT)

    Science.gov (United States)

    In an effort to ensure chemical safety in light of regulatory advances away from reliance on animal testing, USEPA and L’Oréal have collaborated to develop a quantitative systemic toxicity prediction model. Prediction of human systemic toxicity has proved difficult and remains a ...

  14. NATURAL PLANT TOXICANT – CYANOGENIC GLYCOSIDE AMYGDALIN: CHARACTERISTIC, METABOLISM AND THE EFFECT ON ANIMAL REPRODUCTION

    Directory of Open Access Journals (Sweden)

    Eduard Kolesár

    2015-02-01

    Full Text Available The amount of cyanogenic glycosides, as natural plant toxicants, in plants varies with plant species and environmental effects. Cyanogenic glycoside as an amygdalin was detected in apricot kernels, bitter almonds and peach, plum, pear and apple seeds. Amygdalin itself is non-toxic, but its HCN production decomposed by some enzymes is toxic substance. Target of this review was to describe the characteristic, metabolism and possible effects of amygdalin on reproductive processes. Previous studies describe the effects of natural compound amygdalin on female and male reproductive systems focused on process of steroidogenesis, spermatozoa motility and morphological abnormalities of spermatozoa. In accordance to the previous studies on amygdalin its benefit is controversial.

  15. Assessment of toxicity on chelating agent DTPA (diethylenetriaminepentaacetic acid)

    International Nuclear Information System (INIS)

    Fukuda, Satoshi

    1989-01-01

    DTPA (diethylenetriaminepentaacetic acid) is a very important chelating agent to decorporate the radionuclides such as plutonium and americium from human body. However, before DTPA will be administered to humans, the toxicity should be clarified. This report described the summary on data of DTPA toxicities obtained from animal experiments and assessment on the safety for humans, based on the results that compared their data among animal species. In short, Ca-DTPA is less toxic than Zn-DTPA when it is injected intravenously, while Zn-DTPA is less toxic than Ca-DTPA when it is administered orally. Both DTPAs acted on the serum calcium metabolism and induced the functional damages of cardiovascular system. Particularly, it is stressed that Zn-DTPA by intravenous injection occurred the heart failure, increases of blood pressure and pulse with hypocalcemia in even normal rats and beagle dogs. Other side effects by both DTPAs were also observed in the intestine, liver, kidney and bone. It is estimated that there are almost no species differences on DTPA toxicity between animals and humans. As a result, it is concluded that DTPA should be used very carefully for humans, with reference to the results obtained from animal experiments. (author) 61 refs

  16. Assessment of toxicity on chelating agent DTPA (diethylenetriaminepentaacetic acid)

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Satoshi (National Inst. of Radiological Sciences, Chiba (Japan))

    1989-09-01

    DTPA (diethylenetriaminepentaacetic acid) is a very important chelating agent to decorporate the radionuclides such as plutonium and americium from human body. However, before DTPA will be administered to humans, the toxicity should be clarified. This report described the summary on data of DTPA toxicities obtained from animal experiments and assessment on the safety for humans, based on the results that compared their data among animal species. In short, Ca-DTPA is less toxic than Zn-DTPA when it is injected intravenously, while Zn-DTPA is less toxic than Ca-DTPA when it is administered orally. Both DTPAs acted on the serum calcium metabolism and induced the functional damages of cardiovascular system. Particularly, it is stressed that Zn-DTPA by intravenous injection occurred the heart failure, increases of blood pressure and pulse with hypocalcemia in even normal rats and beagle dogs. Other side effects by both DTPAs were also observed in the intestine, liver, kidney and bone. It is estimated that there are almost no species differences on DTPA toxicity between animals and humans. As a result, it is concluded that DTPA should be used very carefully for humans, with reference to the results obtained from animal experiments. (author) 61 refs.

  17. In silico assessment of the acute toxicity of chemicals: recent advances and new model for multitasking prediction of toxic effect.

    Science.gov (United States)

    Kleandrova, Valeria V; Luan, Feng; Speck-Planche, Alejandro; Cordeiro, M Natália D S

    2015-01-01

    The assessment of acute toxicity is one of the most important stages to ensure the safety of chemicals with potential applications in pharmaceutical sciences, biomedical research, or any other industrial branch. A huge and indiscriminate number of toxicity assays have been carried out on laboratory animals. In this sense, computational approaches involving models based on quantitative-structure activity/toxicity relationships (QSAR/QSTR) can help to rationalize time and financial costs. Here, we discuss the most significant advances in the last 6 years focused on the use of QSAR/QSTR models to predict acute toxicity of drugs/chemicals in laboratory animals, employing large and heterogeneous datasets. The advantages and drawbacks of the different QSAR/QSTR models are analyzed. As a contribution to the field, we introduce the first multitasking (mtk) QSTR model for simultaneous prediction of acute toxicity of compounds by considering different routes of administration, diverse breeds of laboratory animals, and the reliability of the experimental conditions. The mtk-QSTR model was based on artificial neural networks (ANN), allowing the classification of compounds as toxic or non-toxic. This model correctly classified more than 94% of the 1646 cases present in the whole dataset, and its applicability was demonstrated by performing predictions of different chemicals such as drugs, dietary supplements, and molecules which could serve as nanocarriers for drug delivery. The predictions given by the mtk-QSTR model are in very good agreement with the experimental results.

  18. Subchronic Toxicity Study of Standardized Methanolic Extract of Mitragyna Speciosa Korth in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Mohd Ulul Ilmie Ahmad Nazri

    2015-06-01

    Full Text Available Mitragyna speciosa Korth, or better known as ketum, has long been used by traditional folk around Southeast Asia to prevent fatigue from working under hot tropical weather and as a replacement of opium, which can then cause addiction. To date, no findings have been reported of the toxic effect of ketum subchronically (28 days. Hence, the aim of this study was to investigate the toxicity of subchronic effect of standardised methanolic extract of ketum (SMEMS in Sprague-Dawley rats. Rats were orally administered with 100, 200, and 500 mg/kg of SMEMS for 28 days. Body weights were recorded daily. They were terminated at day 28 to obtain data for haematology, biochemistry, and histopathology of the brain, liver, kidney, lung, heart, sciatic nerve, and spinal cord. The SMEMS affected body weight compared to control group. Biochemistry findings showed that liver and kidney were affected with the abnormal values in AST, creatinine, globulin, glucose, total protein, and urea. However, SMEMS produced toxic effect more to liver, kidney, and lung than other organs as observed histopathologically. The results suggested subchronic exposure of ketum is toxic to the physiology of the animals.

  19. Addressing the selectivity and toxicity of antiviral nucleosides.

    Science.gov (United States)

    Feng, Joy Y

    2018-01-01

    Nucleoside and nucleotide analogs have played significant roles in antiviral therapies and are valued for their impressive potency and high barrier to resistance. They have been approved for treatment of herpes simplex virus-1, HIV, HBV, HCV, and influenza, and new drugs are being developed for the treatment of RSV, Ebola, coronavirus MERS, and other emerging viruses. However, this class of compounds has also experienced a high attrition rate in clinical trials due to toxicity. In this review, we discuss the utility of different biochemical and cell-based assays and provide recommendations for assessing toxicity liability before entering animal toxicity studies.

  20. Toxic effects of selenium and copper on the planarian, Dugesia dorotocephala

    Energy Technology Data Exchange (ETDEWEB)

    Rauscher, J.D.

    1988-01-01

    Aquatic toxicologists have become increasingly concerned with the effects of sublethal concentrations of toxicants on aquatic organisms. Sublethal effects of toxicants on freshwater invertebrates were reviewed. Selenium (Se) and copper (Cu) are both essential trace elements and toxicants. Se has been reported to alter the toxicity of heavy metals. Planarians, Dugesia dorotocephala, were used as test animals. The objectives of this study were to determine: (1) acute toxicity of Se on planarians and the effect of the number of planarians per test chamber, (2) interaction of the acute toxicity of Se and Cu on planarians, and (3) sublethal effects of Se and Cu on planarians.

  1. Detecting Methemoglobinemia in Animals with a Drop of Blood.

    Directory of Open Access Journals (Sweden)

    Toni G Patton

    Full Text Available A major concern during pesticide development and use is the impact on non-target species, such as raptors or domestic cats and dogs. Sodium nitrite and para-aminopropiophenone (PAPP are two toxicants currently being studied for the control of invasive species, such as starlings and feral swine. When given to an animal these compounds oxidize hemoglobin, which renders it unable to carry oxygen resulting in methemoglobinemia. This study developed a method to estimate methemoglobin levels in mammals and birds by examining the efficacy of sodium nitrite to induce the conversion of hemoglobin to methemoglobin. Varying concentrations of sodium nitrite were added to aliquots of coyote, vole, feral swine, starling, and duck blood, collected from captive animals. The blood samples were analyzed spectrophotometrically to determine percent methemoglobin and digitally to determine red color values (RCV associated with different methemoglobin levels. The avian and mammalian blood reached 100% methemoglobin levels at 200 mM and 15 mM sodium nitrite, respectively. All animals had similar RCV for a given percent methemoglobin. In conclusion, this study developed a procedure to quickly determine methemoglobin levels in mammals and birds. Furthermore, percent methemoglobin can be estimated with one standard curve from any animal species and an image of a blood spot. The technique will be useful during field studies, in agricultural areas, or in a veterinarian's office for the rapid diagnosis of methemoglobinemia in non-target animals that have eaten toxicants/baits or baited animals.

  2. A new mechanism of macrophyte mitigation: how submerged plants reduce malathion's acute toxicity to aquatic animals.

    Science.gov (United States)

    Brogan, William R; Relyea, Rick A

    2014-08-01

    A growing body of evidence suggests that aquatic plants can mitigate the toxicity of insecticides to sensitive aquatic animals. The current paradigm is that this ability is driven primarily by insecticide sorption to plant tissues, especially for hydrophobic compounds. However, recent work shows that submerged plants can strongly mitigate the toxicity of the relatively hydrophilic insecticide malathion, despite the fact that this compound exhibits a slow sorption rate to plants. To examine this disparity, we tested the hypothesis that the mitigating effect of submerged plants on malathion's toxicity is driven primarily by the increased water pH from plant photosynthesis causing the hydrolysis of malathion, rather than by sorption. To do this, we compared zooplankton (Daphnia magna) survival across five environmentally relevant malathion concentrations (0, 1, 4, 6, or 36 μg L(-1)) in test containers where we chemically manipulated water pH in the absence of plants or added the submerged plant (Elodea canadensis) but manipulated plant photosynthetic activity via shading or no shading. We discovered that malathion was equally lethal to Daphnia at all concentrations tested when photosynthetically inactive (i.e. shaded) plants were present (pH at time of dosing=7.8) or when pH was chemically decreased (pH=7.7). In contrast, when photosynthetically active (i.e. unshaded) plants were present (pH=9.8) or when pH was chemically increased (pH=9.5), the effects of 4 and 6 μg L(-1) of malathion on Daphnia were mitigated strongly and to an equal degree. These results demonstrate that the mitigating effect of submerged plants on malathion's toxicity can be explained entirely by a mechanism of photosynthesizing plants causing an increase in water pH, resulting in rapid malathion hydrolysis. Our findings suggest that current ecotoxicological models and phytoremediation strategies may be overlooking a critical mechanism for mitigating pesticides. Copyright © 2014 Elsevier Ltd

  3. Toxic effects of fluoride on organisms.

    Science.gov (United States)

    Zuo, Huan; Chen, Liang; Kong, Ming; Qiu, Lipeng; Lü, Peng; Wu, Peng; Yang, Yanhua; Chen, Keping

    2018-04-01

    Accumulation of excess fluoride in the environment poses serious health risks to plants, animals, and humans. This endangers human health, affects organism growth and development, and negatively impacts the food chain, thereby affecting ecological balance. In recent years, numerous studies focused on the molecular mechanisms associated with fluoride toxicity. These studies have demonstrated that fluoride can induce oxidative stress, regulate intracellular redox homeostasis, and lead to mitochondrial damage, endoplasmic reticulum stress and alter gene expression. This paper reviews the present research on the potential adverse effects of overdose fluoride on various organisms and aims to improve our understanding of fluoride toxicity. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. The detrimental effects of lead on human and animal health

    Directory of Open Access Journals (Sweden)

    Mohammed Abdulrazzaq Assi

    2016-06-01

    Full Text Available Lead, a chemical element in the carbon group with symbol Pb (from Latin: Plumbum, meaning “the liquid silver” and has an atomic number 82 in the periodic table. It was the first element that was characterized by its kind of toxicity. In animal systems, lead (Pb has been incriminated in a wide spectrum of toxic effects and it is considered one of the persistent ubiquitous heavy metals. Being exposed to this metal could lead to the change of testicular functions in human beings as well as in the wildlife. The lead poising is a real threat to the public health, especially in the developing countries. Accordingly, great efforts on the part of the occupational and public health have been taken to curb the dangers of this metal. Hematopoietic, renal, reproductive, and central nervous system are among the parts of the human body and systems that are vulnerable toward the dangers following exposure to high level of Pb. In this review, we discussed the massive harmful impact that leads acetate toxicity has on the animals and the worrying fact that this harmful toxicant can be found quite easily in the environment and abundance. Highlighting its (Pb effects on various organs in the biological systems, its economic, as well as scientific importance, with the view to educate the public/professionals who work in this area. In this study, we focus on the current studies and research related to lead toxicity in animals and also to a certain extent toward human as well.

  5. Gentamicin nephrotoxicity: Animal experimental correlate with human pharmacovigilance outcome

    Directory of Open Access Journals (Sweden)

    Olufunsho Awodele

    2015-04-01

    Full Text Available Background: National Agency for Food and Drugs Administration and Control (NAFDAC, which is responsible for pharmacovigilance activity in Nigeria, recently withdrew injection gentamicin 280 mg, used in the management of life-threatening and multidrug-resistant infections from circulation, due to reported toxicity. Thus, this study aimed to investigate the toxicity profile of the commonly used strengths (80 mg and 280 mg of gentamicin on kidney using animal models. Methods: Animals were divided into five groups of 16 rats each. For rats of groups 1 and 2, gentamicin (1.14 mg/kg each group was administered intramuscularly twice daily for 7 and 14 days, respectively, after which eight of them were sacrificed by cervical dislocation. Blood was collected via cardiac puncture and the kidneys were carefully removed and weighed immediately. The remaining eight animals were kept for reversibility study for another 7 and 14 days, respectively. For groups 3 and 4, gentamicin (4 mg/kg each group was administered as a single daily dose for 7 and 14 days, respectively, and eight animals from the groups were subjected to reversibility study for 7 and 14 days, respectively. Group 5, the control group animals, were given 10 ml/kg distilled water for 14 days. Histopathology of the kidneys, serum creatinine levels, and antioxidant enzyme activities were investigated. Results: Significant increase (p ≤ 0.001 in the level of creatinine of rats administered 4.0 mg/kg for 14 days was observed compared with all other groups. Significant (p ≤ 0.001 elevations in the lipid peroxidation in all gentamicin-administered animals and acute tubular necrosis in most of the gentamicin-administered animals were observed. Conclusion: Toxicity profile of gentamicin on the kidneys is dependent on both dose and duration of administration. The findings justify the decision made by NAFDAC to ban the use of high-dose inj. gentamicin 280 mg in Nigeria.

  6. Toxicity of pyrolysis gases from polyether sulfone

    Science.gov (United States)

    Hilado, C. J.; Olcomendy, E. M.

    1979-01-01

    A sample of polyether sulfone was evaluated for toxicity of pyrolysis gases, using the toxicity screening test method developed at the University of San Francisco. Animal response times were relatively short at pyrolysis temperatures of 600 to 800 C, with death occurring within 6 min. The principal toxicant appeared to be a compound other than carbon monoxide.

  7. Nanosilica and Polyacrylate/Nanosilica: A Comparative Study of Acute Toxicity

    Directory of Open Access Journals (Sweden)

    Ying-Mei Niu

    2016-01-01

    Full Text Available We compared the acute toxicity of nanosilica and polyacrylate/nanosilica instillation in Wistar rats (n=60. Exposure to nanosilica and polyacrylate/nanosilica showed a 30% mortality rate. When compared with saline-treated rats, animals in both exposure groups exhibited a significant reduction of PO2 (P<0.05 at both 24 and 72 hr. after exposure. Both exposure groups exhibited a significant reduction of neutrophils in arterial blood compared to saline controls (P<0.05 24 hr. after exposure. The levels of blood ALT and LDH in exposed groups were found to be significantly increased (P<0.05 24 hr. following exposure. The exposed groups exhibited various degrees of pleural effusion and pericardial effusion. Our findings indicated respiratory exposure to polyacrylate/nanosilica and nanosilica is likely to cause multiple organ toxicity.

  8. Exploring the impact of toxic attitudes and a toxic environment on the veterinary healthcare team

    Directory of Open Access Journals (Sweden)

    Irene eMoore

    2015-12-01

    Full Text Available AbstractThe objective of this qualitative study was to compare veterinarians’ and Registered Veterinary Technicians’ (RVT’s perceptions of the veterinary health care team with respect to the impact of toxic attitudes and a toxic environment. Focus group interviews using a semi-structured interview guide and follow up probes were held with 4 veterinarian groups (23 companion animal veterinarians and 4 Registered Veterinary Technician groups (26 RVTs. Thematic analysis of the discussions indicated both veterinarian and RVT participants felt team members with toxic attitudes negatively impacted veterinary team function. These attitudes included people being disrespectful, being resistant to change, always wanting to be the go to person, avoiding conflict, and lacking motivation. When conflict was ignored, or when people with toxic attitudes were not addressed, a toxic environment often resulted. A toxic environment sometimes manifested when broken communication and tension between staff members occurred as a result of employees lacking confidence, skills, or knowledge not being managed properly. It also occurred when employees did not feel appreciated, when there was difficulty coping with turnover, and when there were conflicting demands.The presence of people with a toxic attitude was a source of frustration for both veterinarian and RVT participants. Prompt and consistent attention to negative behaviors is recommended to reduce the development of a toxic environment.

  9. Toxicity studies of the water extract from the calyces of Hibiscus sabdariffa L. in rats.

    Science.gov (United States)

    Sireeratawong, Seewaboon; Itharat, Arunporn; Khonsung, Parirat; Lertprasertsuke, Nirush; Jaijoy, Kanjana

    2013-01-01

    Acute and chronic toxicities of the water extract from calyces of Hibiscus sabdariffa were studied in male and female rats. After 14 days of a single oral administration of test substance 5,000 mg/kg body weight, measurement of the body and organ weights, necropsy and health monitoring were performed. No signs and differences of the weights or behaviour compared to the control rats were observed. The results indicated that the single oral administration of H. sabdariffa extract in the amount of 5,000 mg/kg body weight does not produce acute toxicity. The chronic toxicity was determined by oral feeding both male and female rats daily with the extract at the doses of 50, 100, and 200 mg/kg body weight for 270 days. The examinations of signs, animal behaviour and health monitoring showed no defects in the test groups compared to the control groups. Both test and control groups (day 270th) and satellite group (day 298th) were analysed by measuring their final body and organ weights, taking necropsy, and examining haematology, blood clinical chemistry, and microanatomy. Results showed no differences from the control groups. Overall, our study demonstrated that an oral administration of H. sabdariffa extract at the doses of 50, 100 and 200 mg/kg body weight for 270 days does not cause chronic toxicity in rat.

  10. Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of 177Lu-EDTMP, a potential bone pain palliation agent

    International Nuclear Information System (INIS)

    Mathe, Domokos; Balogh, Lajos; Polyak, Andras; Kiraly, Reka; Marian, Terez; Pawlak, Dariusz; Zaknun, John J.; Pillai, Maroor R.A.; Janoki, Gyozo A.

    2010-01-01

    Introduction: Radionuclide therapy (RNT) is an effective method for bone pain palliation in patients suffering from bone metastasis. Due to the long half-life, easy production and relatively low β- energy, 177 Lu [T 1/2 =6.73 days, E βmax =497 keV, E γ =113 keV (6.4%), 208 keV (11%)]-based radiopharmaceuticals offer logistical advantage for wider use. This paper reports the results of a multispecies biodistribution and toxicity studies of 177 Lu-EDTMP to collect preclinical data for starting human clinical trials. Methods: 177 Lu-EDTMP with radiochemical purity greater than 99% was formulated by using a lyophilized kit of EDTMP (35 mg of EDTMP, 5.72 g of CaO and 14.1 mg of NaOH). Biodistribution studies were conducted in mice and rabbits. Small animal imaging was performed using NanoSPECT/CT (Mediso, Ltd., Hungary) and digital autoradiography. Gamma camera imaging was done in rabbits and dogs. Four levels of activity (9.25 through 37 MBq/kg body weight) of 177 Lu-EDTMP were injected in four groups of three dogs each to study the toxicological effects. Results: 177 Lu-EDTMP accumulated almost exclusively in the skeletal system (peak ca. 41% of the injected activity in bone with terminal elimination half-life of 2130 and 1870 h in mice and rabbits, respectively) with a peak uptake during 1-3 h. Excretion of the radiopharmaceutical was through the urinary system. Imaging studies showed that all species (mouse, rat, rabbit and dog) take up the compound in regions of remodeling bone, while kidney retention is not visible after 1 day postinjection (pi). In dogs, the highest applied activity (37 MBq/kg body weight) led to a moderate decrease in platelet concentration (mean, 160 g/L) at 1 week pi with no toxicity. Conclusion: The protracted effective half-life of 177 Lu-EDTMP in bone supports that modifying the EDTMP molecule by introducing 177 Lu does not alter its biological behaviour as a specific bone-seeking tracer. Species-specific pharmacokinetic behavior

  11. Reproductive toxicity in boron exposed workers in Bandirma, Turkey.

    Science.gov (United States)

    Başaran, Nurşen; Duydu, Yalçin; Bolt, Hermann M

    2012-06-01

    Boric acid and sodium borates have been considered as being "toxic to reproduction and development", following results of animal studies with high doses. However unfavorable effects of boron exposure on reproduction and development have not been proved in epidemiological studies so far. The aim of the present study was to investigate the reproductive toxicity indicators in highly exposed workers employed in a boric acid production plant in Bandırma, Turkey. Two hundred and four workers participated in this study. The mean blood boron concentration of the high exposure group of workers was 223.89 ± 69.49 (152.82-454.02)ng/g. Unfavorable effects of boron exposure on the reproductive toxicity indicators were not observed. Copyright © 2012 Elsevier GmbH. All rights reserved.

  12. Baltimore Air Toxics Study (BATS)

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, D.A. [Sullivan Environmental Consulting, Inc., Alexandria, VA (United States)

    1996-12-31

    The Baltimore Air Toxics Study is one of the three urban air toxics initiatives funded by EPA to support the development of the national air toxics strategy. As part of this project, the Air Quality Integrated Management System (AIMS) is under development. AIMS is designed to bring together the key components of urban air quality management into an integrated system, including emissions assessment, air quality modeling, and air quality monitoring. Urban area source emissions are computed for a wide range of pollutants and source categories, and are joined with existing point source emissions data. Measured air quality data are used to evaluate the adequacy of the emissions data and model treatments as a function of season, meteorological parameters, and daytime/nighttime conditions. Based on tested model performance, AIMS provides the potential to improve the ability to predict air quality benefits of alternative control options for criteria and toxic air pollutants. This paper describes the methods used to develop AIMS, and provides examples from its application in the Baltimore metropolitan area. The use of AIMS in the future to enhance environmental management of major industrial facilities also will be addressed in the paper.

  13. Toxicity of middle distillates from dermal exposure.

    Science.gov (United States)

    Koschier, F J

    1999-02-01

    This report focuses on recent studies that investigated the effects of kerosine dermal exposure on neurotoxicity and reproductive/developmental toxicity. Background toxicity information will also be reviewed for kerosine range mid distillates. The kerosine range mid distillates have a carbon range of C9-C16 and have a boiling range of 302-554 degrees F (150-290 degrees C). This category includes kerosine, aviation fuels (e.g., Jet A, JP-5 and JP-8), no. 1 fuel oil and diesel fuel oil. In general, the kerosine range mid distillates demonstrate relatively low acute toxicity by any route of exposure. High inhalation exposures can induce central nervous system depression characterized by ataxia, hypoactivity and prostration. Kerosines are known to cause skin irritation and inflammation under conditions of acute and repeated exposure in animals and humans, but are only slightly irritating to the eye and are not skin sensitizers. In addition, the absorption of kerosine range mid distillates through the skin has been demonstrated to be fairly rapid, but limited to approximately 10-15% of the applied dose after 24 hours. The kerosine range mid distillates are generally inactive in genetic toxicity tests although positive studies have been reported. Positive results, while at times equivocal, have been reported for straight run kerosine and jet fuel A in the mouse lymphoma assay with metabolic activation, and hydrodesulfurized kerosine (mouse) and jet fuel A (rat) in the bone marrow cytogenetic assay. Effects on the nervous and reproductive systems have been reported in humans and experimental animals under conditions where inhalation and dermal exposure to specific kerosine type fuels are sometimes difficult to separate. Recent laboratory studies have addressed this point and examined the effects of dermal exposure. In these studies, rats were exposed to hydrodesulfurized kerosine by skin application to determine the potential of dermal contact to cause reproductive

  14. Subchronic (26- and 52-week) toxicity and irritation studies of a novel microbicidal gel formulation containing sodium lauryl sulfate in animal models.

    Science.gov (United States)

    Piret, Jocelyne; Laforest, Geneviève; Bussières, Martin; Bergeron, Michel G

    2008-03-01

    The safety of an ethylene oxide/propylene oxide gel formulation containing sodium lauryl sulfate (2%, w/w), that could be a potent candidate as a topical microbicide, has been evaluated. More specifically, the subchronic (26- and 52-week) toxicity of the formulation when applied intravaginally as well as its irritating potential for the rectal, penile, eye, skin and buccal mucosa have been examined in animal models. The results showed that the vaginal administration of the gel formulation containing sodium lauryl sulfate once and twice daily (with doses 12 +/- 2 h apart) for 26 weeks to rats and for 52 weeks to rabbits induced slight to moderate histopathological alterations. When the formulation was applied intrarectally to male and female rabbits once and twice daily (with doses 12 +/- 2 h apart) for 14 days, no macroscopic or microscopic changes were reported. For both vaginal and rectal dosing, no effect was seen on the haematology, coagulation and serum chemistry parameters as well as on the body weight of animals and the relative organ weights. Other sporadic macroscopic and histopathological findings were incidental in origin and of no toxicological significance. The gel formulation containing sodium lauryl sulfate was considered as mildly irritating for the penile mucosa of rabbits, non-irritating for the eye of rabbits, mildly irritating for the skin in a rabbit model and non-irritating for the hamster cheek pouch. It is suggested that the gel formulation containing sodium lauryl sulfate is safe for most tissues that could be exposed to the product under normal use.

  15. The fish embryo toxicity test as an animal alternative method in hazard and risk assessment and scientific research

    International Nuclear Information System (INIS)

    Embry, Michelle R.; Belanger, Scott E.; Braunbeck, Thomas A.; Galay-Burgos, Malyka; Halder, Marlies; Hinton, David E.; Leonard, Marc A.; Lillicrap, Adam; Norberg-King, Teresa; Whale, Graham

    2010-01-01

    Animal alternatives research has historically focused on human safety assessments and has only recently been extended to environmental testing. This is particularly for those assays that involve the use of fish. A number of alternatives are being pursued by the scientific community including the fish embryo toxicity (FET) test, a proposed replacement alternative to the acute fish test. Discussion of the FET methodology and its application in environmental assessments on a global level was needed. With this emerging issue in mind, the ILSI Health and Environmental Sciences Institute (HESI) and the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) held an International Workshop on the Application of the Fish Embryo Test as an Animal Alternative Method in Hazard and Risk Assessment and Scientific Research in March, 2008. The workshop included approximately 40 scientists and regulators representing government, industry, academia, and non-governmental organizations from North America, Europe, and Asia. The goal was to review the state of the science regarding the investigation of fish embryonic tests, pain and distress in fish, emerging approaches utilizing fish embryos, and the use of fish embryo toxicity test data in various types of environmental assessments (e.g., hazard, risk, effluent, and classification and labeling of chemicals). Some specific key outcomes included agreement that risk assessors need fish data for decision-making, that extending the FET to include eluethereombryos was desirable, that relevant endpoints are being used, and that additional endpoints could facilitate additional uses beyond acute toxicity testing. The FET was, however, not yet considered validated sensu OECD. An important action step will be to provide guidance on how all fish tests can be used to assess chemical hazard and to harmonize the diverse terminology used in test guidelines adopted over the past decades. Use of the FET in context of effluent assessments

  16. The fish embryo toxicity test as an animal alternative method in hazard and risk assessment and scientific research

    Energy Technology Data Exchange (ETDEWEB)

    Embry, Michelle R., E-mail: membry@ilsi.org [ILSI Health and Environmental Sciences Institute, 1156 15th Street, NW, Suite 200, Washington, DC 20005 (United States); Belanger, Scott E., E-mail: belanger.se@pg.com [Procter and Gamble, Central Product Safety, PO Box 538707, Miami Valley Innovation Center, Cincinnati, OH 45253-8707 (United States); Braunbeck, Thomas A., E-mail: braunbeck@zoo.uni-heidelberg.de [University of Heidelberg, Im Neuenheimer Feld 230, Heidelberg D -69120 (Germany); Galay-Burgos, Malyka, E-mail: malyka.galay-burgos@ecetoc.org [European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), 4 Avenue E. Van Nieuwenhuyse B-1160, Brussels (Belgium); Halder, Marlies, E-mail: marlies.halder@jrc.ec.europa.eu [European Commission, Joint Research Centre, Institute for Health and Consumer Protection, In-Vitro Methods Unit TP-580 Ispra 21027 (Italy); Hinton, David E., E-mail: dhinton@duke.edu [Duke University, Nicholas School of the Environment, PO Box 90328, Durham, NC 27708, Unites States (United States); Leonard, Marc A., E-mail: mleonard@rd.loreal.com [L' Oreal Recherche Avancee, Unite d' Ecotoxicologie, 1 av. E. Schueller, 93601 Aulnay sous bois (France); Lillicrap, Adam, E-mail: Adam.lillicrap@niva.no [AstraZeneca, Freshwater Quarry, Brixham TQ5 8BA (United Kingdom); Norberg-King, Teresa, E-mail: norberg-king.teresa@epa.gov [U.S. EPA, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, MN 55804-1636 (United States); Whale, Graham, E-mail: graham.whale@shell.com [Shell Global Solutions, Analytical Technology, P.O. Box 1, Chester CH1 3SH (United Kingdom)

    2010-04-15

    Animal alternatives research has historically focused on human safety assessments and has only recently been extended to environmental testing. This is particularly for those assays that involve the use of fish. A number of alternatives are being pursued by the scientific community including the fish embryo toxicity (FET) test, a proposed replacement alternative to the acute fish test. Discussion of the FET methodology and its application in environmental assessments on a global level was needed. With this emerging issue in mind, the ILSI Health and Environmental Sciences Institute (HESI) and the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) held an International Workshop on the Application of the Fish Embryo Test as an Animal Alternative Method in Hazard and Risk Assessment and Scientific Research in March, 2008. The workshop included approximately 40 scientists and regulators representing government, industry, academia, and non-governmental organizations from North America, Europe, and Asia. The goal was to review the state of the science regarding the investigation of fish embryonic tests, pain and distress in fish, emerging approaches utilizing fish embryos, and the use of fish embryo toxicity test data in various types of environmental assessments (e.g., hazard, risk, effluent, and classification and labeling of chemicals). Some specific key outcomes included agreement that risk assessors need fish data for decision-making, that extending the FET to include eluethereombryos was desirable, that relevant endpoints are being used, and that additional endpoints could facilitate additional uses beyond acute toxicity testing. The FET was, however, not yet considered validated sensu OECD. An important action step will be to provide guidance on how all fish tests can be used to assess chemical hazard and to harmonize the diverse terminology used in test guidelines adopted over the past decades. Use of the FET in context of effluent assessments

  17. Gossypol Toxicity from Cottonseed Products

    Directory of Open Access Journals (Sweden)

    Ivana Cristina N. Gadelha

    2014-01-01

    Full Text Available Gossypol is a phenolic compound produced by pigment glands in cotton stems, leaves, seeds, and flower buds (Gossypium spp.. Cottonseed meal is a by-product of cotton that is used for animal feeding because it is rich in oil and proteins. However, gossypol toxicity limits cottonseed use in animal feed. High concentrations of free gossypol may be responsible for acute clinical signs of gossypol poisoning which include respiratory distress, impaired body weight gain, anorexia, weakness, apathy, and death after several days. However, the most common toxic effects is the impairment of male and female reproduction. Another important toxic effect of gossypol is its interference with immune function, reducing an animal’s resistance to infections and impairing the efficiency of vaccines. Preventive procedures to limit gossypol toxicity involve treatment of the cottonseed product to reduce the concentration of free gossypol with the most common treatment being exposure to heat. However, free gossypol can be released from the bound form during digestion. Agronomic selection has produced cotton varieties devoid of glands producing gossypol, but these varieties are not normally grown because they are less productive and are more vulnerable to attacks by insects.

  18. Toxicity studies on the radioprotective agent WR-2721 in CDF1 mice and beagle dogs

    International Nuclear Information System (INIS)

    Palmer, T.E.; Glaza, S.M.; Dickie, B.C.; Weltman, R.H.; Greenspun, K.S.

    1985-01-01

    WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid, is used extensively to protect normal cells during the irradiation of neoplastic cells. Dose levels for human radiotherapy are based on results obtained from laboratory animal lethality and toxicity studies. WR-2721 was administered intravenously to CDF1 mice and beagle dogs. Single dose lethality studies in mice showed the average 1/10 of the lethal dose, the median lethal dose and 9/10 the lethal dose to be 508 (1523 mg/m2), 589 (1766 mg/m2), and 682 mg/kg (2047 mg/m2), respectively. The lethal dose for female mice was lower than that for males. The 1/10 lethal dose in mice was slightly toxic to dogs; 1/10 of that dose was nontoxic. The lethal dose for dogs (6000 mg/m2) was higher than that for mice (2000 mg/m2). Clinical signs of toxicosis in the single-dose mouse toxicity study were evident in the 1st week following treatment and declined during the recovery period; signs of toxicosis were transient in dogs. Acute drug-induced pathologic changes included elevated BUN and SGOT levels, lymphoid necrosis, and renal tubular degeneration in mice. These changes were evident in the 1st week following treatment, but had dissipated by study termination. Generalized vascular changes (congestion, hemorrhage, and edema) and renal tubular degeneration occurred in treated dogs that had died or were killed moribund 7 days postinjection. These findings indicate sex-dependent and interspecies variation in the toxicity of WR-2721 with acute, but reversible, pathologic changes

  19. Molecular basis of cadmium toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Nath, R; Prasad, R; Palinal, V K; Chopra, R K

    1984-01-01

    Cadmium has been shown to manifest its toxicity in human and animals by mainly accumulating in almost all of the organs. The kidney is the main target organ where it is concentrated mainly in the cortex. Environmental exposure of cadmium occurs via food, occupational industries, terrestrial and aquatic ecosystem. At molecular level, cadmium interferes with the utilization of essential metals e.g. Ca, Zn, Se, Cr and Fe and deficiencies of these essential metals including protein and vitamins, exaggerate cadmium toxicity, due to its increased absorption through the gut and greater retention in different organs as metallothionein (Cd-Mt). Cadmium transport, across the intestinal and renal brush border membrane vesicles, is carrier mediated and it competes with zinc and calcium. It has been postulated that cadmium shares the same transport system. Cadmium inhibits protein synthesis, carbohydrate metabolism and drug metabolizing enzymes in liver of animals. Chronic environmental exposure of cadmium produces hypertension in experimental animals. Functional changes accompanying cadmium nephropathy include low molecular weight proteinuria which is of tubular origin associated with excess excretion of proteins such as beta 2 microglobulin, metallothionein and high molecular weight proteinuria of glomerular origin (excretion of proteins such as albumin IgG, transferrin etc.). Recent data has shown that metallothionein is more nephrotoxic to animals. Cadmium is also toxic to central nervous system. It causes an alterations of cellular functions in lungs. Cadmium affects both humoral and cell mediated immune response in animals. Cadmium induces metallothionein in liver and kidney but under certain nutritional deficiencies like protein-calorie malnutrition and calcium deficiency, enhanced induction and greater accumulation of cadmium metallothionein has been observed.

  20. Meta-analysis of toxicity and teratogenicity of 133 chemicals from zebrafish developmental toxicity studies

    Science.gov (United States)

    Zebrafish developmental toxicity testing is an emerging field, which faces considerable challenges regarding data meta-analysis and the establishment of standardized test protocols. Here, we present an initial correlation study on toxicity of 133 chemicals based on data in the li...

  1. WE-AB-207B-10: On Spinal Nerve Toxicity from Single-Session SAbR in Pigs and the Translation of Small Animal NTCP Models

    Energy Technology Data Exchange (ETDEWEB)

    Hrycushko, B; Medin, P [UT Southwestern Medical Center, Dallas, TX (United States)

    2016-06-15

    Purpose: The incidence of peripheral neuropathy has risen with increased utilization of SAbR. There is no consensus regarding the dose-tolerance of the peripheral nervous system. In 2015, we commenced an investigation to test the hypotheses that single-session irradiation to the pig spinal nerves exhibit a similar dose-tolerance as that of the spinal cord and that a dose-length effect exists. This work evaluates the direct application of small animal NTCP models to both large animal spinal cord and preliminary peripheral nerve data. Methods: To date, 16 of 25 Yucatan minipigs have received single-session SAbR to a 1.5cm length and 4 of 25 have received irradiation to a 0.5cm length of left-sided C6-C8 spinal nerves. Toxicity related gait change has been observed in 13 animals (9 from the long length group and 4 from the short). This preliminary data is overlaid on several dose-response models which have been fit to rodent spinal cord tolerance experiments. Model parameters define a toxicity profile between a completely serial or parallel behaving organ. Adequacy of model application, including how length effects are handled, to published minipig spinal cord dose-response data and to preliminary peripheral nerve response data was evaluated through residual analysis. Results: No rodent-derived dose-response models were directly applicable to all pig data for the different lengths irradiated. Several models fit the long-length irradiated spinal cord data well, with the more serial-like models fitting best. Preliminary data on the short-length irradiation suggests no length effect exists, disproving our hypothesis. Conclusion: Direct application of small-animal NTCP models to pig data suggests dose-length effect predictions from small animal data may not translate clinically. However, the small animal models used have not considered dose heterogeneity and it is expected that including the low-to-mid dose levels in the penumbral region will improve this match. This work

  2. WE-AB-207B-10: On Spinal Nerve Toxicity from Single-Session SAbR in Pigs and the Translation of Small Animal NTCP Models

    International Nuclear Information System (INIS)

    Hrycushko, B; Medin, P

    2016-01-01

    Purpose: The incidence of peripheral neuropathy has risen with increased utilization of SAbR. There is no consensus regarding the dose-tolerance of the peripheral nervous system. In 2015, we commenced an investigation to test the hypotheses that single-session irradiation to the pig spinal nerves exhibit a similar dose-tolerance as that of the spinal cord and that a dose-length effect exists. This work evaluates the direct application of small animal NTCP models to both large animal spinal cord and preliminary peripheral nerve data. Methods: To date, 16 of 25 Yucatan minipigs have received single-session SAbR to a 1.5cm length and 4 of 25 have received irradiation to a 0.5cm length of left-sided C6-C8 spinal nerves. Toxicity related gait change has been observed in 13 animals (9 from the long length group and 4 from the short). This preliminary data is overlaid on several dose-response models which have been fit to rodent spinal cord tolerance experiments. Model parameters define a toxicity profile between a completely serial or parallel behaving organ. Adequacy of model application, including how length effects are handled, to published minipig spinal cord dose-response data and to preliminary peripheral nerve response data was evaluated through residual analysis. Results: No rodent-derived dose-response models were directly applicable to all pig data for the different lengths irradiated. Several models fit the long-length irradiated spinal cord data well, with the more serial-like models fitting best. Preliminary data on the short-length irradiation suggests no length effect exists, disproving our hypothesis. Conclusion: Direct application of small-animal NTCP models to pig data suggests dose-length effect predictions from small animal data may not translate clinically. However, the small animal models used have not considered dose heterogeneity and it is expected that including the low-to-mid dose levels in the penumbral region will improve this match. This work

  3. Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition.

    Science.gov (United States)

    Sørli, Jorid B; Huang, Yishi; Da Silva, Emilie; Hansen, Jitka S; Zuo, Yi Y; Frederiksen, Marie; Nørgaard, Asger W; Ebbehøj, Niels E; Larsen, Søren T; Hougaard, Karin S

    2018-01-01

    Private consumers and professionals may experience acute inhalation toxicity after inhaling aerosolized impregnation products. The distinction between toxic and non-toxic products is difficult to make for producers and product users alike, as there is no clearly described relationship between the chemical composition of the products and induction of toxicity. The currently accepted method for determination of acute inhalation toxicity is based on experiments on animals; it is time-consuming, expensive and causes stress for the animals. Impregnation products are present on the market in large numbers and amounts and exhibit great variety. Therefore, an alternative method to screen for acute inhalation toxicity is needed. The aim of our study was to determine if inhibition of lung surfactant by impregnation products in vitro could accurately predict toxicity in vivo in mice. We tested 21 impregnation products using the constant flow through set-up of the constrained drop surfactometer to determine if the products inhibited surfactant function or not. The same products were tested in a mouse inhalation bioassay to determine their toxicity in vivo. The sensitivity was 100%, i.e., the in vitro method predicted all the products that were toxic for mice to inhale. The specificity of the in vitro test was 63%, i.e., the in vitro method found three false positives in the 21 tested products. Six of the products had been involved in accidental human inhalation where they caused acute inhalation toxicity. All of these six products inhibited lung surfactant function in vitro and were toxic to mice.

  4. Acute and subchronic toxicity study of the water extract from root of Imperata cylindrica (Linn. Raeusch. in rats

    Directory of Open Access Journals (Sweden)

    Siharat Chunlaratthanaphorn

    2007-03-01

    Full Text Available The water extract from root of Imperata cylindrica (Linn. Raeusch. was studied for acute and subchronic toxicities. The extract at a single dose of 5,000 mg/kg was administered orally to female and male rats (5 male, 5 female. After 14 days, signs and behavioral changes, mortality, gross and histopathological changes of internal organs were examined. The extract did not produce signs of toxicity. For the subchronic toxicity test, the extract at doses of 300, 600 and 1,200 mg/kg body weight was orally administered to rats daily for 90 days (10 male, 10 female. The observation of signs, behavior and health status showed no abnormality in the test groups as compared with the controls. At the end of the study, necropsy and histopathology examination were performed in all animals in the control group, the test groups and the satellite group in which the extract was discontinued for another 28 days. Body and organ weights, hematological and blood clinical chemistry were also examined. The results suggest that the water extract of Imperata cylindrica (Linn. Raeusch does not cause acute and subchronic toxicities in rats.

  5. Reproductive toxicity of carbon nanomaterials: a review

    Science.gov (United States)

    Vasyukova, I.; Gusev, A.; Tkachev, A.

    2015-11-01

    In the current review, we assembled the experimental evidences of an association between carbon nanomaterials including carbon black, graphite nanoplatelets, graphene, single- and multi-walled carbon nanotubes, and fullerene exposure and adverse reproductive and developmental effects, in vitro and in vivo studies. It is shown that carbon nanomaterials reveal toxic effect on reproductive system and offspring development of the animals of various system groups to a certain degree depending on carbon crystal structure. Although this paper provides initial information about the potential male and female reproductive toxicity of carbon nanomaterials, further studies, using characterized nanoparticles, relevant routes of administration, and doses closely reflecting all the expected levels of exposure are needed.

  6. Poisoning of domestic animals with heavy metals

    Directory of Open Access Journals (Sweden)

    Velev Romel

    2009-01-01

    Full Text Available The term heavy metal refers to a metal that has a relatively high density and is toxic for animal and human organism at low concentrations. Heavy metals are natural components of the Earth's crust. They cannot be degraded or destroyed. To a small extent they enter animal organism via food, drinking water and air. Some heavy metals (e.g cooper, iron, chromium, zinc are essential in very low concentrations for the survival of all forms of life. These are described as essential trace elements. However, when they are present in greater quantities, like the heavy metals lead, cadmium and mercury which are already toxic in very low concentrations, they can cause metabolic anomalies or poisoning. Heavy metal poisoning of domestic animals could result, for instance, from drinking-water contamination, high ambient air concentrations near emission sources, or intake via the food chain. Heavy metals are dangerous because they tend to bioaccumulate in a biological organism over time. Manifestation of toxicity of individual heavy metals varies considerably, depending on dose and time of exposure, species, gender and environmental and nutritional factors. Large differences exist between the effects of a single exposure to a high concentration, and chronic exposures to lower doses. The aim of this work is to present the source of poisoning and toxicity of some heavy metals (lead, mercury, cadmium, thallium, arsenic, as well as new data about effects of those heavy metals on the health of domestic animals. .

  7. Sponge-Associated Bacteria Produce Non-cytotoxic Melanin Which Protects Animal Cells from Photo-Toxicity.

    Science.gov (United States)

    Vijayan, Vijitha; Jasmin, Chekidhenkuzhiyil; Anas, Abdulaziz; Parakkaparambil Kuttan, Sreelakshmi; Vinothkumar, Saradavey; Perunninakulath Subrayan, Parameswaran; Nair, Shanta

    2017-09-01

    Melanin is a photo-protective polymer found in many organisms. Our research shows that the bacteria associated with darkly pigmented sponges (Haliclona pigmentifera, Sigmadocia pumila, Fasciospongia cavernosa, Spongia officinalis, and Callyspongia diffusa) secrete non-cytotoxic melanin, with antioxidant activity that protects animal cells from photo-toxicity. Out of 156 bacterial strains screened, 22 produced melanin and these melanin-producing bacteria (MPB) were identified as Vibrio spp., Providencia sp., Bacillus sp., Shewanella sp., Staphylococcus sp., Planococcus sp., Salinococcus sp., and Glutamicibacter sp. Maximum melanin production was exhibited by Vibrio alginolyticus Marine Microbial Reference Facility (MMRF) 534 (50 mg ml -1 ), followed by two isolates of Vibrio harveyi MMRF 535 (40 mg ml -1 ) and MMRF 546 (30 mg ml -1 ). Using pathway inhibition assay and FT-IR spectral analysis, we identified the melanin secreted into the culture medium of MPB as 1,8-dihydroxynaphthalene-melanin. The bacterial melanin was non-cytotoxic to mouse fibroblast L929 cells and brine shrimps up to a concentration of 200 and 500 ppm, respectively. Bacterial melanin showed antioxidant activity at very low concentration (IC 50 -9.0 ppm) and at 50 ppm, melanin protected L929 cells from UV-induced intracellular reactive oxygen stress. Our study proposes sponge-associated bacteria as a potential source of non-cytotoxic melanin with antioxidant potentials.

  8. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on behavior

    International Nuclear Information System (INIS)

    Mullenix, P.J.; Kernan, W.J.; Tassinari, M.S.; Schunior, A.; Waber, D.P.; Howes, A.; Tarbell, N.J.

    1990-01-01

    Central nervous system prophylactic therapy used in the treatment of acute lymphoblastic leukemia can reduce intelligence quotient scores and impair memory and attention in children. Cranial irradiation, intrathecal methotrexate, and steroids are commonly utilized in acute lymphoblastic leukemia therapy. How they induce neurotoxicity is unknown. This study employs an animal model to explore the induction of neurotoxicity. Male and female Sprague-Dawley rats at 17 and 18 days of age were administered 18 mg/kg prednisolone, 2 mg/kg methotrexate, and 1000 cGy cranial irradiation. Another 18-day-old group was administered 1000 cGy cranial irradiation but no drugs. Matching controls received saline and/or a sham exposure to radiation. All animals at 6 weeks and 4 months of age were tested for alterations in spontaneous behavior. A computer pattern recognition system automatically recorded and classified individual behavioral acts displayed during exploration of a novel environment. Measures of behavioral initiations, total time, and time structure were used to compare treated and control animals. A permanent sex-specific change in the time structure of behavior was induced by the prednisolone, methotrexate, and radiation treatment but not by radiation alone. Unlike hyperactivity, the effect consisted of abnormal clustering and dispersion of acts in a pattern indicative of disrupted development of sexually dimorphic behavior. This study demonstrates the feasibility of an animal model delineating the agent/agents responsible for the neurotoxicity of central nervous system prophylactic therapy

  9. Some similarities of radium and plutonium toxicity in the beagle and man

    International Nuclear Information System (INIS)

    Taylor, G.N.; Jee, W.S.S.; Mays, C.W.

    1976-01-01

    The value of many toxicity studies, involving various experimental animals, is contingent on how reliably the data can be related to man. An equation has been proposed for extrapolating the Pu syndrome from dog studies to man. It employs the extensive human radium experience and a plutonium-radium toxicity ratio in the dog. The validity of this method is contingent on similar target tissues for both Pu and Ra and approximately equal RBE's for Pu relative to Ra in both man and the dog. Thus, although the radiosensitivity might be significantly different, the endpoints within a given tissue in man and the animal model must necessarily be comparative. The degree of parallelism in the radium-induced syndromes of man and the beagle are examined in order to assess the practicability of estimating Pu risk in man through use of a Pu-Ra toxicity ratio in the beagles

  10. Acute and sub-chronic oral toxicity studies of erythritol in Beagle dogs.

    Science.gov (United States)

    Eapen, Alex K; de Cock, Peter; Crincoli, Christine M; Means, Charlotte; Wismer, Tina; Pappas, Christopher

    2017-07-01

    Polyols, also known as sugar alcohols, are widely used in the formulation of tooth-friendly and reduced-calorie foods. Considering the significant health benefits of polyols in products formulated for human use, there is increased interest in evaluating potential uses in companion animal applications. Erythritol and xylitol are two polyols which are currently widely used in products ranging from reduced-sugar foods to personal care and cosmetics. Published studies have shown that both of these compounds are well-tolerated in rodents. Their toxicity profiles differ when comparing canine safety data. Doses of xylitol as low as 0.15 g/kg-BW in dogs can result in life-threatening hypoglycemia and acute liver failure, whereas erythritol is well-tolerated in dogs with reported No Adverse Effect Levels upwards of 5 g/kg-BW/day in repeat-dose studies. While pivotal studies substantiating the safe use of erythritol in humans have been published, there are limited published studies to support the safe use of erythritol in dogs. Here we present the results of an acute oral and a sub-chronic oral toxicity study in Beagle dogs. Given the potential health benefits of oral products formulated with erythritol and the data presented herein substantiating the safe use in dogs, erythritol can be safely used in products for canines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Animal Studies of Addictive Behavior

    Science.gov (United States)

    Ahmed, Serge H.

    2013-01-01

    It is increasingly recognized that studying drug taking in laboratory animals does not equate to studying genuine addiction, characterized by loss of control over drug use. This has inspired recent work aimed at capturing genuine addiction-like behavior in animals. In this work, we summarize empirical evidence for the occurrence of several DSM-IV-like symptoms of addiction in animals after extended drug use. These symptoms include escalation of drug use, neurocognitive deficits, resistance to extinction, increased motivation for drugs, preference for drugs over nondrug rewards, and resistance to punishment. The fact that addiction-like behavior can occur and be studied in animals gives us the exciting opportunity to investigate the neural and genetic background of drug addiction, which we hope will ultimately lead to the development of more effective treatments for this devastating disorder. PMID:23249442

  12. Trichothecenes: structure-toxic activity relationships.

    Science.gov (United States)

    Wu, Qinghua; Dohnal, Vlastimil; Kuca, Kamil; Yuan, Zonghui

    2013-07-01

    Trichothecenes comprise a large family of structurally related toxins mainly produced by fungi belonging to the genus Fusarium. Among trichothecenes, type A and type B are of the most concern due to their broad and highly toxic nature. In order to address structure-activity relationships (SAR) of trichothecenes, relationships between structural features and biological effects of trichothecene mycotoxins in mammalian systems are summarized in this paper. The double bond between C-9-C-10 and the 12,13-epoxide ring are essential structural features for trichothecene toxicity. Removal of these groups results in a complete loss of toxicity. A hydroxyl group at C-3 enhances trichothecene toxicity, while this activity decreases gradually when C-3 is substituted with either hydrogen or an acetoxy group. The presence of a hydroxyl group at C-4 promotes slightly lower toxicity than an acetoxy group at the same position. The toxicity for type B trichothecenes decreases if the substituent at C-4 is changed from acetoxy to hydroxyl or hydrogen at C-4 position. The presence of hydroxyl and hydrogen groups on C-15 decreases the trichothecene toxicity in comparison with an acetoxy group attached to this carbon. Trichothecenes toxicity increases when a macrocyclic ring exists between the C-4 and C-15. At C-8 position, an oxygenated substitution at C-8 is essential for trichothecene toxicity, indicating a decrease in the toxicity if substituent change from isovaleryloxy through hydrogen to the hydroxyl group. The presence of a second epoxy ring at C-7-C-8 reduces the toxicity, whereas epoxidation at C-9-C-10 of some macrocyclic trichothecenes increases the activity. Conjugated trichothecenes could release their toxic precursors after hydrolysis in animals, and present an additional potential risk. The SAR study of trichothecenes should provide some crucial information for a better understanding of trichothecene chemical and biological properties in food contamination.

  13. Medical Applications and Toxicities of Gallium Compounds

    Directory of Open Access Journals (Sweden)

    Christopher R. Chitambar

    2010-05-01

    Full Text Available Over the past two to three decades, gallium compounds have gained importance in the fields of medicine and electronics. In clinical medicine, radioactive gallium and stable gallium nitrate are used as diagnostic and therapeutic agents in cancer and disorders of calcium and bone metabolism. In addition, gallium compounds have displayed anti-inflammatory and immunosuppressive activity in animal models of human disease while more recent studies have shown that gallium compounds may function as antimicrobial agents against certain pathogens. In a totally different realm, the chemical properties of gallium arsenide have led to its use in the semiconductor industry. Gallium compounds, whether used medically or in the electronics field, have toxicities. Patients receiving gallium nitrate for the treatment of various diseases may benefit from such therapy, but knowledge of the therapeutic index of this drug is necessary to avoid clinical toxicities. Animals exposed to gallium arsenide display toxicities in certain organ systems suggesting that environmental risks may exist for individuals exposed to this compound in the workplace. Although the arsenic moiety of gallium arsenide appears to be mainly responsible for its pulmonary toxicity, gallium may contribute to some of the detrimental effects in other organs. The use of older and newer gallium compounds in clinical medicine may be advanced by a better understanding of their mechanisms of action, drug resistance, pharmacology, and side-effects. This review will discuss the medical applications of gallium and its mechanisms of action, the newer gallium compounds and future directions for development, and the toxicities of gallium compounds in current use.

  14. Animal Exposure During Burn Tests

    Science.gov (United States)

    Gaume, J. G.

    1978-01-01

    An animal exposure test system (AETS) was designed and fabricated for the purpose of collecting physiological and environmental (temperature) data from animal subjects exposed to combustion gases in large scale fire tests. The AETS consisted of an open wire mesh, two-compartment cage, one containing an exercise wheel for small rodents, and the other containing one rat instrumented externally for electrocardiogram (ECG) and respiration. Cage temperature is measured by a thermistor located in the upper portion of the rat compartment. Animal activity is monitored by the ECG and the records indicate an increase in EMG (electromyograph) noise super-imposed by the increased activity of the torso musculature. Examples of the recordings are presented and discussed as to their significance regarding toxicity of fire gases and specific events occurring during the test. The AETS was shown to be a useful tool in screening materials for the relative toxicity of their outgassing products during pyrolysis and combustion.

  15. Safety assessment of Superba™ krill powder: Subchronic toxicity study in rats

    Directory of Open Access Journals (Sweden)

    Kjetil Berge

    2015-01-01

    Full Text Available The safety of krill powder was assessed in a subchronic 13-week toxicity study where rats were fed krill powder or control diets. The krill powder inclusion in the test diet was 9.67% (w/w. There were no differences noted in body weight or food consumption in either gender. Differences in clinical chemistry values were noted in the krill powder-treated animals, but these findings were of no toxicological significance. A significant decrease in absolute heart weight, but not relative heart weight, was observed in both sexes given krill powder, although no corresponding histological changes were observed. Hepatocyte vacuolation was noted histologically in males fed krill powder. This finding was not associated with other indications of hepatic dysfunction. The no observed adverse effect level (NOAEL for the conditions of this study was considered to be 9.67% krill powder.

  16. Biocombatibility and in vivo toxicity assessment of multilayered polymer encapsulated lanthanide doped particles

    International Nuclear Information System (INIS)

    Dhanya, C.R.; Sri Sivakumar; Jaishree, J.; Abraham, Annie

    2013-01-01

    Layer-by-layer (LbL) deposition technique has led to the development of multilayered multifunctional nanoparticles that can prove to be promising system for directed drug delivery. Recently, surface functionalized Lanthanide doped nanoparticles have been explored as a candidate for biomedical applications like bio-detection, fluorescence imaging and drug delivery. The toxicity behaviors of biomedical devices proposed for therapeutic use in human must be checked for their toxicity behaviors in animal models. Here, we have presented an initial systematic animal toxicity study of polymer encapsulated lanthanide doped particle in Swiss Albino mice. Polymer coated LNPs with concentration of 100 nM in PBS was administered intravenously through tail vein according to body weight (4μl/g). Animal behavior, survival and animal mass, were monitored and evaluated over short-term (one week) and long-term (one month) periods, after which animals were euthanized. Blood was collected for evaluating clinical biochemistry (SGOT and SGPT) and hematological parameters, and tissues (liver and kidney) for organ histology. Results demonstrated normal serum clinical biochemistry in animals for both short and long time exposure. Histological examination of LNP treated mice also showed normal histology of liver and kidney even after one month of administration. Similar results were obtained for hematological evaluation. Results exhibited the systemic nontoxic nature of the polymer encapsulated lanthanide particles and their suitability as a tool for tumor targeted drug delivery. (author)

  17. Toxicity of Pesticides. Agrichemical Fact Sheet 2.

    Science.gov (United States)

    Hock, Winand K.

    This fact sheet gives the acute oral and dermal toxicity (LD 50) of over 250 pesticides in lab animals. The chemicals are categorized as fungicides, herbicides, insecticides, or miscellaneous compounds. One or more trade names are given for each pesticide. In addition, a brief explanation of toxicity determination is given. (BB)

  18. Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of {sup 177}Lu-EDTMP, a potential bone pain palliation agent

    Energy Technology Data Exchange (ETDEWEB)

    Mathe, Domokos [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary)], E-mail: mdomokos@hp.osski.hu; Balogh, Lajos; Polyak, Andras; Kiraly, Reka [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary); Marian, Terez [Institute of Nuclear Medicine, Debrecen University, Debrecen (Hungary); Pawlak, Dariusz [Institute of Atomic Energy, Radioisotope Centre POLATOM, Swierk-Otwock (Poland); Zaknun, John J.; Pillai, Maroor R.A. [International Atomic Energy Agency (IAEA), Vienna (Austria); Janoki, Gyozo A. [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary)

    2010-02-15

    Introduction: Radionuclide therapy (RNT) is an effective method for bone pain palliation in patients suffering from bone metastasis. Due to the long half-life, easy production and relatively low {beta}- energy, {sup 177}Lu [T{sub 1/2}=6.73 days, E{sub {beta}}{sub max}=497 keV, E{sub {gamma}}=113 keV (6.4%), 208 keV (11%)]-based radiopharmaceuticals offer logistical advantage for wider use. This paper reports the results of a multispecies biodistribution and toxicity studies of {sup 177}Lu-EDTMP to collect preclinical data for starting human clinical trials. Methods: {sup 177}Lu-EDTMP with radiochemical purity greater than 99% was formulated by using a lyophilized kit of EDTMP (35 mg of EDTMP, 5.72 g of CaO and 14.1 mg of NaOH). Biodistribution studies were conducted in mice and rabbits. Small animal imaging was performed using NanoSPECT/CT (Mediso, Ltd., Hungary) and digital autoradiography. Gamma camera imaging was done in rabbits and dogs. Four levels of activity (9.25 through 37 MBq/kg body weight) of {sup 177}Lu-EDTMP were injected in four groups of three dogs each to study the toxicological effects. Results: {sup 177}Lu-EDTMP accumulated almost exclusively in the skeletal system (peak ca. 41% of the injected activity in bone with terminal elimination half-life of 2130 and 1870 h in mice and rabbits, respectively) with a peak uptake during 1-3 h. Excretion of the radiopharmaceutical was through the urinary system. Imaging studies showed that all species (mouse, rat, rabbit and dog) take up the compound in regions of remodeling bone, while kidney retention is not visible after 1 day postinjection (pi). In dogs, the highest applied activity (37 MBq/kg body weight) led to a moderate decrease in platelet concentration (mean, 160 g/L) at 1 week pi with no toxicity. Conclusion: The protracted effective half-life of {sup 177}Lu-EDTMP in bone supports that modifying the EDTMP molecule by introducing {sup 177}Lu does not alter its biological behaviour as a specific bone

  19. Toxic potential of palytoxin.

    Science.gov (United States)

    Patocka, Jiří; Gupta, Ramesh C; Wu, Qing-hua; Kuca, Kamil

    2015-10-01

    This review briefly describes the origin, chemistry, molecular mechanism of action, pharmacology, toxicology, and ecotoxicology of palytoxin and its analogues. Palytoxin and its analogues are produced by marine dinoflagellates. Palytoxin is also produced by Zoanthids (i.e. Palythoa), and Cyanobacteria (Trichodesmium). Palytoxin is a very large, non-proteinaceous molecule with a complex chemical structure having both lipophilic and hydrophilic moieties. Palytoxin is one of the most potent marine toxins with an LD50 of 150 ng/kg body weight in mice exposed intravenously. Pharmacological and electrophysiological studies have demonstrated that palytoxin acts as a hemolysin and alters the function of excitable cells through multiple mechanisms of action. Palytoxin selectively binds to Na(+)/K(+)-ATPase with a Kd of 20 pM and transforms the pump into a channel permeable to monovalent cations with a single-channel conductance of 10 pS. This mechanism of action could have multiple effects on cells. Evaluation of palytoxin toxicity using various animal models revealed that palytoxin is an extremely potent neurotoxin following an intravenous, intraperitoneal, intramuscular, subcutaneous or intratracheal route of exposure. Palytoxin also causes non-lethal, yet serious toxic effects following dermal or ocular exposure. Most incidents of palytoxin poisoning have manifested after oral intake of contaminated seafood. Poisonings in humans have also been noted after inhalation, cutaneous/systemic exposures with direct contact of aerosolized seawater during Ostreopsis blooms and/or through maintaining aquaria containing Cnidarian zoanthids. Palytoxin has a strong potential for toxicity in humans and animals, and currently this toxin is of great concern worldwide.

  20. Collaborative work on evaluation of ovarian toxicity. 13) Two- or four-week repeated dose studies and fertility study of PPAR alpha/gamma dual agonist in female rats.

    Science.gov (United States)

    Sato, Norihiro; Uchida, Keisuke; Nakajima, Mikio; Watanabe, Atsushi; Kohira, Terutomo

    2009-01-01

    The main focus of this study was to determine the optimal dosing period in a repeated dose toxicity study based on toxic effects as assessed by ovarian morphological changes. To assess morphological and functional changes induced in the ovary by a peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual agonist, the compound was administered to female rats at dose levels of 0, 4, 20, and 100 mg/kg/day in a repeated dose toxicity study for 2 or 4 weeks, and from 2 weeks prior to mating to Day 7 of pregnancy in a female fertility study. In the repeated dose toxicity study, an increase in atresia of large follicles, a decrease in corpora lutea, and an increase in stromal cells were observed in the treated groups. In addition, the granulosa cell exfoliations into antrum of large follicles and corpora lutea with retained oocyte are morphological characteristics induced by this compound, and they might be related with abnormal condition of ovulation. In the female fertility study, the pregnancy rate tended to decrease in the 100 mg/kg/day group. At necropsy, decreases in the number of corpora lutea, implantations and live embryos were noted in the 20 and 100 mg/kg/day group. No changes were observed in animals given 4 mg/kg/day. These findings indicated that histopathological changes in the ovary are important endpoints for evaluation of drugs inducing ovarian damage. In conclusion, a 2-week administration period is sufficient to detect ovarian toxicity of this test compound in the repeated dose toxicity study.

  1. The Occurrence and Toxicity of Indospicine to Grazing Animals

    Directory of Open Access Journals (Sweden)

    Mary T. Fletcher

    2015-07-01

    Full Text Available Indospicine is a non-proteinogenic amino acid which occurs in Indigofera species with widespread prevalence in grazing pastures across tropical Africa, Asia, Australia, and the Americas. It accumulates in the tissues of grazing livestock after ingestion of Indigofera. It is a competitive inhibitor of arginase and causes both liver degeneration and abortion. Indospicine hepatoxicity occurs universally across animal species but the degree varies considerably between species, with dogs being particularly sensitive. The magnitude of canine sensitivity is such that ingestion of naturally indospicine-contaminated horse and camel meat has caused secondary poisoning of dogs, raising significant industry concern. Indospicine impacts on the health and production of grazing animals per se has been less widely documented. Livestock grazing Indigofera have a chronic and cumulative exposure to this toxin, with such exposure experimentally shown to induce both hepatotoxicity and embryo-lethal effects in cattle and sheep. In extensive pasture systems, where animals are not closely monitored, the resultant toxicosis may well occur after prolonged exposure but either be undetected, or even if detected not be attributable to a particular cause. Indospicine should be considered as a possible cause of animal poor performance, particularly reduced weight gain or reproductive losses, in pastures where Indigofera are prevalent.

  2. An evaluation of acute toxicity of colloidal silver nanoparticles.

    Science.gov (United States)

    Maneewattanapinyo, Pattwat; Banlunara, Wijit; Thammacharoen, Chuchaat; Ekgasit, Sanong; Kaewamatawong, Theerayuth

    2011-11-01

    Tests for acute oral toxicity, eye irritation, corrosion and dermal toxicity of colloidal silver nanoparticles (AgNPs) were conducted in laboratory animals following OECD guidelines. Oral administration of AgNPs at a limited dose of 5,000 mg/kg produced neither mortality nor acute toxic signs throughout the observation period. Percentage of body weight gain of the mice showed no significant difference between control and treatment groups. In the hematological analysis, there was no significant difference between mice treated with AgNPs and controls. Blood chemistry analysis also showed no differences in any of the parameter examined. There was neither any gross lesion nor histopathological change observed in various organs. The results indicated that the LD(50) of colloidal AgNPs is greater than 5,000 mg/kg body weight. In acute eye irritation and corrosion study, no mortality and toxic signs were observed when various doses of colloidal AgNPs were instilled in guinea pig eyes during 72 hr observation period. However, the instillation of AgNPs at 5,000 ppm produced transient eye irritation during early 24 hr observation time. No any gross abnormality was noted in the skins of the guinea pigs exposed to various doses of colloidal AgNPs. In addition, no significant AgNPs exposure relating to dermal tissue changes was observed microscopically. In summary, these findings of all toxicity tests in this study suggest that colloidal AgNPs could be relatively safe when administered to oral, eye and skin of the animal models for short periods of time.

  3. Comparative studies on plasma mineral status of cattle in fluoride toxic brackish water zone of Punjab, India

    Directory of Open Access Journals (Sweden)

    Sushma Chhabra

    2012-05-01

    Full Text Available Objective: Chronic fluoride intoxication or fluorosis is a worldwide health problem in humans and animals. The present research work was aimed to assess the status of copper, zinc, cobalt, manganese, magnesium, calcium and phosphorus in blood of fluorotic cattle in brackish water zone of Punjab. Methods: The present study was conducted in villages of district Muktsar, a brackish water zone, of Punjab state. Cattle (n=103 showing signs of dental lesions or lameness, from the villages with water fluoride concentration more than 1 ppm, were selected for the study whereas cattle (n=98 from villages with water fluoride concentration less than 1 ppm and with no clinical signs served as control. Blood samples were collected from both the groups and were analysed for minerals.Results: Significantly (P<0.05 higher plasma F concentrations were observed in animals of fluorotic region in comparison to healthy control animals. Concentrations of plasma Ca, Mg, Cu and Zn were significantly lower in cattle of hydrofluorotic region. Plasma phosphorus, iron and iodine concentrations were higher in animals of hydrofluorotic region whereas Mo and Mn did not differ between the two groups. Conclusions: Present study indicated decrease in certain essential minerals in animals of fluorotic region and such changes may contribute to the toxic effects associated with exposure to excess fluoride and salinity

  4. New EPA Guidance for Testing Pesticides Will Reduce Animal Testing

    Science.gov (United States)

    EPA is issuing guidance for requesting waivers of acute dermal toxicity testing requirements for pesticide formulations, which will lead to fewer animal tests for acute dermal toxicity for pesticides.

  5. Skin toxicity of jet fuels: ultrastructural studies and the effects of substance P

    International Nuclear Information System (INIS)

    Monteiro-Riviere, Nancy A.; Inman, Alfred O.; Riviere, Jim E.

    2004-01-01

    Topical exposure to jet fuel is a significant occupational hazard. Recent studies have focused on dermal absorption of fuel and its components, or alternatively, on the biochemical or immunotoxicological sequelae to exposure. Surprisingly, morphological and ultrastructural analyses have not been systematically conducted. Similarly, few studies have compared responses in skin to that of the primary target organ, the lung. The focus of the present investigation was 2-fold: first, to characterize the ultrastructural changes seen after topical exposure to moderate doses (335 or 67 μl/cm 2 ) of jet fuels [Jet A, Jet Propellant (JP)-8, JP-8+100] for up to 4 days in pigs, and secondly, to determine if co-administration of substance P (SP) with JP-8 jet fuel in human epidermal keratinocyte cell cultures modulates toxicity as it does to pulmonary toxicity in laboratory animal studies. The primary change seen after exposure to all fuels was low-level inflammation accompanied by formation of lipid droplets in various skin layers, mitochondrial and nucleolar changes, cleft formation in the intercellular lipid lamellar bilayers, as well as disorganization in the stratum granulosum-stratum corneum interface. An increased number of Langerhans cells were also noted in jet fuel-treated skin. These changes suggest that the primary effect of jet fuel exposure is damage to the stratum corneum barrier. SP administration decreased the release of interleukin (IL)-8 normally seen in keratinocytes after JP-8 exposure, a response similar to that reported for SP's effect on JP-8 pulmonary toxicity. These studies provide a base upon which biochemical and immunological data collected in other model systems can be compared

  6. A 13-week toxicity study of acrylamide administered in drinking water to hamsters.

    Science.gov (United States)

    Imai, Toshio; Kitahashi, Tsukasa

    2014-01-01

    Acrylamide (AA) is known to induce tumors in various organs/tissues in rats and mice. Epidemiological studies of oral exposure have generated controversial results but mortality studies of people who work with AA have indicated increased rates of pancreatic cancer. In the present study, for dose selection for chronic toxicity/carcinogenicity studies, 13-week toxicity of AA was evaluated in Syrian hamsters, which are sensitive to induction of pancreatic ductal carcinogenesis, at concentrations required to provide doses of 0 (control), 20, 30 and 50 mg kg(-1) body weight in drinking water. Treatment with AA caused abnormal gait advancing to hind limb paralysis in all males and females at 50 mg kg(-1). Body weights in 30 and 50 mg kg(-1) males and 50 mg kg(-1) females were lower than in the controls. At termination of the study, red blood cells (RBC) and hemoglobin (Hb) were decreased or showed a tendency for a decrease at 20 and 30 mg kg(-1) in females. Microscopically, axonal/myelin degeneration of sciatic nerves was observed in all AA-treated groups with dose dependence. No obvious changes were found in pancreatic ducts/ductules in any groups of animal. These results indicated the maximum tolerated dose for long-term studies of AA to be 20 mg kg(-1) or less in both male and female Syrian hamsters. Copyright © 2012 John Wiley & Sons, Ltd.

  7. Animal use in the chemical and product manufacturing sectors - can the downtrend continue?

    Science.gov (United States)

    Curren, Rodger

    2009-12-01

    During the 1990s and early 2000s, a number of manufacturing companies in the cosmetic, personal care and household product industries were able to substantially reduce their use of animals for testing (or to not use animals in the first place). These reductions were almost always the result of significant financial contributions to either direct, in-house alternatives research, or to support personnel whose duties were to understand and apply the current state-of-the-art for in vitro testing. They occurred almost exclusively in non-regulatory areas, and primarily involved acute topical toxicities. Over the last few years, the reduction in animal use has been much less dramatic, because some companies are still reluctant to change from the traditional animal studies, because systemic, repeat-dose toxicity is more difficult to model in vitro, and because many products still require animal testing for regulatory approval. Encouragingly, we are now observing an increased acceptance of non-animal methods by regulatory agencies. This is due to mounting scientific evidence from larger databases, agreement by companies to share data and testing strategies with regulatory agencies, and a focus on smaller domains of applicability. These changes, along with new emphasis and financial support for addressing systemic toxicities, promise to provide additional possibilities for industry to replace animals with in vitro methods, alone or in combination with in silico methods. However, the largest advance will not occur until more companies commit to using the non-animal test strategies that are currently available. 2009 FRAME.

  8. Toxicity of inhaled alpha-emitting radionuclides - Status report

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Mewhinney, J.A.; Guilmette, R.A.; Gillett, N.A.; Diel, J.H.; Lundgren, D.L.; Hahn, F.F.; Boecker, B.B.; McClellan, R.O.

    1988-01-01

    The toxicity of inhaled alpha-emitting radionuclides is being investigated in a series of interrelated dose-response studies. Dogs, rodents, and nonhuman primates have been exposed to monodisperse or polydisperse aerosols of the oxides of 239 Pu, 238 Pu, 241 Am, or 244 Cm to measure the relative importance of average organ dose, local dose around particles, specific activity, chemical form, particle size, and number of particles inhaled to the development of biological effects. The influence of animal species, age at exposure, and pre-existing lung disease, as well as the effects of repeated exposure, are also being studied, because they may influence the toxicity of these radionuclides. (author)

  9. One Health and Toxic Cyanobacteria | Science Inventory | US ...

    Science.gov (United States)

    One Health and toxic cyanobacteria Blooms of toxic freshwater blue-green algae or cyanobacteria (HABs) have been in the news after HABs associated with human and animal health problems have been reported in Florida, California and Utah during 2016. HABs occur in warm, slow moving or stagnant surface waters that are enriched with nutrients such as nitrogen and phosphorous. People are exposed to potentially toxic HABs during recreation in contaminated water, after exposure to contaminated drinking water or to blue-green algae supplements. Animals may be exposed to toxic HABs after drinking contaminated surface waters or coming into contact with HABs then ingesting cyanobacteria from their bodies during self-grooming activities. As HABs are being reported more frequently in the US, it is important for veterinarians to secure good exposure histories and to recognize the potential signs and health consequences of HAB exposures. We will review the current knowledge about human and animal health effects associated with freshwater HABs and scenarios that pose the highest risks for illnesses and deaths. This abstract does not necessarily reflect EPA policy. This is a summary of One Health and Cyanobacteria for public health and public practice veterinarians at the American Veterinary Medical Association annual convention. This product is associated with SSWR 4.01B

  10. Toxicity of heavy metals to fish: an important consideration for sucessful aquaculture

    OpenAIRE

    Nnaji, J.C.; Okoye, F.C.

    2007-01-01

    Heavy metals are toxic to man, animals and plants once safe limits are exceeded. Then ability to bio accumulate in plant and animal tissues makes them particularly hazardous. Heavy metals are toxic to all aquatic biota and cause high mortality of fish larva, fry, fingerling and adult fish. They accumulate in the gills, heart, liver, kidneys, brain, bones and muscles of fish. The physico-chemical forms of heavy metals determine their mobility, availability and toxicity to fish. These metals en...

  11. Investigation of animal and algal bioassays for reliable saxitoxin ecotoxicity and cytotoxicity risk evaluation.

    Science.gov (United States)

    Perreault, François; Matias, Marcelo Seleme; Melegari, Silvia Pedroso; Pinto, Catia Regina Silva de Carvalho; Creppy, Edmond Ekué; Popovic, Radovan; Matias, William Gerson

    2011-05-01

    Contamination of water bodies by saxitoxin can result in various toxic effects in aquatic organisms. Saxitoxin contamination has also been shown to be a threat to human health in several reported cases, even resulting in death. In this study, we evaluated the sensitivity of animal (Neuro-2A) and algal (Chlamydomonas reinhardtii) bioassays to saxitoxin effect. Neuro-2A cells were found to be sensitive to saxitoxin, as shown by a 24 h EC50 value of 1.5 nM, which was obtained using a cell viability assay. Conversely, no saxitoxin effect was found in any of the algal biomarkers evaluated, for the concentration range tested (2-128 nM). These results indicate that saxitoxin may induce toxic effects in animal and human populations at concentrations where phytoplankton communities are not affected. Therefore, when evaluating STX risk of toxicity, algal bioassays do not appear to be reliable indicators and should always be conducted in combination with animal bioassays. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. The sea urchin, a versatile model for eco-toxicity studies and ecological experimental research

    Directory of Open Access Journals (Sweden)

    D. Privitera

    2011-01-01

    Full Text Available Echinoderm early developmental stages represent a good tool for toxicity testing in different fields, ranging from environment to food contamination, and in full respect of the 3Rs objectives (Reduction, Refinement, Replacement of animal experiments, that will lead to the reduction of vertebrate use for toxicity testing. Further, sea urchins are key species in a wide range of marine habitats, as they are able to structure algal community. Experiments and observations aiming at the  characterization of anthropogenic or climate changes effects on their settlement, population structure, feeding behaviour and reproductive condition, may be useful to describe future scenarios regarding the whole marine community. The present paper represents a short review of the possible applications of eco-toxicity bioassays using Paracentrotus lividus gametes and embryos. Further, examples of ecological researches, involving sea urchins, aiming at the definition of future scenarios will be preserved.

  13. Evaluation of Cardiopulmonary Toxicity Following Oral Administration of Multi-walled Carbon Nanotubes in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Ehsan Zayerzadeh

    2016-07-01

    Full Text Available Objective(s: Carbon nanotubes have unique mechanical, electrical, and thermal properties, with potential different applications in nanomedicine, electronics, and other industries. These new applications of carbon nanotubes in different industries lead to the increased exposure risk of nanomaterials to human. Up to now, all aspects of carbon nanotubes toxicity are not completely clear following human and animal exposures with these novel compounds. The aim of this study was to assess cardiopulmonary toxicity of multi-walled carbon nanotubes following oral administration in rats with respect to the histopathological and biochemical evaluation. Methods: In the present investigation, we studied cardiorespiratory toxicity of multi-wall carbon nanotubes (MWCNT with regard to histopathological changes and some biomarkers including TnT, CK-MB and LDH in experimental rats following oral administration. One dose per 24 h of MWCNT suspension was administered orally (gavage technique to animals at the doses of 500, 1000 and 2000 mg/kg/day BW for 5 days. Results: The results of these study showed oral administration of MWCNT induces histopathological complications such as severe alveolar edema and hemorrhage in lungs and myocytolysis in heart of all experimental groups of animals. In all of the groups, troponin T level showed no changes when compared to baseline. Lactate dehydrogenase and CK-MB activity showed significant increment in all of animal groups following oral administration of carbon nanotubes. Conclusions: It can be concluded that oral exposure of MWCNT may be toxic for cardiovascular and respiratory systems, because MWCNT induced biochemical alterations and histopathological abnormalities in these vital systems.

  14. Present status of radiation treatment of animal feeds in Japan

    International Nuclear Information System (INIS)

    Ito, H.; Iizuka, H.

    1979-01-01

    This paper summarizes the studies in Japan on the irradiation of laboratory animal diets and farm animal feedstuffs. From the microbiological inactivation curve of laboratory animal diets, the irradiation doses of 2.5 approximately 3.5 Mrad seem to be suitable for sterilization of animal diets. The absence of toxic effects on animals can be demonstrated by feeding studies. The elimination of salmonellae and other species of Enterobacteriaceae in feedstuffs could be achieved by irradiation with 0.5 approximately 0.6 Mrad. The growth of moulds in feeds would not occur at this dose level. However, an adverse effect is observed on chicks fed with fatty diet irradiated at 3 and 6 Mrad. It is suggested that a promising application of radiation treatment to the feeding of farm animals is irradiation at low dose levels of 0.5 approximately 0.6 Mrad. (author)

  15. Comparative systemic toxicity of ropivacaine and bupivacaine in nonpregnant and pregnant ewes.

    Science.gov (United States)

    Santos, A C; Arthur, G R; Wlody, D; De Armas, P; Morishima, H O; Finster, M

    1995-03-01

    Ropivacaine is a new amide local anesthetic, having therapeutic properties similar to those of bupivacaine but with a wider margin of safety. Bupivacaine is probably the most commonly used drug in obstetric epidural analgesia, even though laboratory studies have suggested that pregnancy increases the cardiotoxicity of bupivacaine but not of other local anesthetics. The current study was designed to reevaluate, in a random and blinded fashion, the systemic toxicity of bupivacaine and ropivacaine in nonpregnant and pregnant sheep. Chronically prepared nonpregnant and pregnant ewes were randomized to receive an intravenous infusion of ropivacaine or bupivacaine at a constant rate of 0.5 mg.kg-1.min-1 until circulatory collapse. The investigators were blinded to the identity of local anesthetic. Heart rate, arterial blood pressure, and cardiac rhythm were monitored throughout the study. Arterial blood samples were obtained before infusion and at the onset of toxic manifestations, which appeared in the following sequence: convulsions, hypotension, apnea, and circulatory collapse. Serum drug concentrations and protein binding were determined. Blood pH and gas tensions were measured. There were no significant differences between non-pregnant and pregnant animals in the doses or serum concentrations of either drug required to elicit toxic manifestations. In nonpregnant animals, similar doses and serum concentrations of ropivacaine and bupivacaine were associated with the onset of convulsions and circulatory collapse. In pregnant ewes, greater doses of ropivacaine as compared to bupivacaine were required to produce convulsions (7.5 +/- 0.5 vs. 5.0 +/- 0.6 mg.kg-1) and circulatory collapse (12.9 +/- 0.8 vs. 8.5 +/- 1.2 mg.kg-1). The corresponding serum concentrations of ropivacaine were similar to those of bupivacaine. Pregnancy did not affect the serum protein binding of either drug. The proportion of animals manifesting a malignant ventricular arrhythmia as the terminal

  16. Transformation of toxic potential of Jatropha curcas (Ratanjyot into protein source: A mini-review

    Directory of Open Access Journals (Sweden)

    Amit Shukla

    2015-06-01

    Full Text Available The production of animal largely depends on supplying of quality feed and proteinaceous supplement to the animals. Jatropha plant can grow in the barren lands, and are used as a source of biodiesel. Besides, the plant may act as a rich proteinaceous source. However, the antinutritional factors present in the seed and seed oil of the plant may hamper the availability and beneficial use of the plant. Curcin and phorbol esters are the major toxic compounds present in the plant; these toxic compounds cause to produce liver and kidney diseases. Detoxification of these toxic compounds by physical and chemical means converting to less toxic seed cake may serve the purpose of using this plant in future as a replacement of costly protein supplement for animals. Therefore, in modern world, it is recommended to utilize the protein source by neutralizing the antinutritional factors. This mini-review describes the updates on how J. curcas can be utilized as a supplementary source of protein for animals by decreasing its toxicity.

  17. Functional toxicology: tools to advance the future of toxicity testing

    Science.gov (United States)

    Gaytán, Brandon D.; Vulpe, Chris D.

    2014-01-01

    The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds—information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes. PMID:24847352

  18. Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

    Science.gov (United States)

    Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

    2014-08-01

    Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Acute and subacute toxicity of 18F-FDG

    International Nuclear Information System (INIS)

    Dantas, Danielle M.; Silva, Natanael G. da; Manetta, Ana Paula; Osso Junior, Joao A.

    2013-01-01

    Before initiating clinical trials of a new drug, it is necessary to perform a battery of safety tests, for evaluating the risk in humans. Radiopharmaceuticals must be tested taking into account its specificity, duration of treatment and especially the toxicity of both, the unlabelled molecule and its radionuclide, apart from impurities emanating from radiolysis. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when ANVISA established the Resolutions No. 63, which refers to the Good Manufacturing Practices of radiopharmaceuticals and No. 64 which seeks the registration of radiopharmaceuticals. Nowadays IPEN produces one of the most important radiopharmaceutical for nuclear medicine, the 18 F-FDG, which is used in the diagnosis. The objective of this study is to assess systemic toxicity (acute / subacute) of 18 F-FDG in an in vivo test system, as recommended by the RDC No. 64. In acute tests the administration occurred on the first day, healthy rats were observed for 14 days reporting their clinical signs and water consumption, and on the 15th day they were euthanized and necropsied. The assay of subacute toxicity observations were made over a period of 28 days and the first dose was administered at the beginning of the test and after a fortnight a second dose was administered. The parameters evaluated were the necropsy, histopathology of target organs, hematology studies and liver and kidney function. The results are being processed and evaluated. Initial observations did not show any acute toxicity in animals when compared to control animals. (author)

  20. Acute and subchronic toxicity study of the water extract from dried fruits of Piper nigrum L. in rats

    Directory of Open Access Journals (Sweden)

    Kanjana Jaijoy

    2007-03-01

    Full Text Available The study was carried out to evaluate acute and subchronic toxicities of the water extract from the dried fruits of Piper nigrum L. A single oral administration of the extract at a dose of 5,000 mg/kg body weight (5 male, 5 female did not produce signs of toxicity, behavioral changes, mortality, changes on gross appearance or histopathological changes of internal organs. The subchronic toxicity was determined by oral feeding both male and female rats (10 male, 10 female daily with the test substance at the doses of 300, 600 and 1,200 mg/kg body weight continuously for 90 days. The examinations of signs, animal behavior and health monitoring showed no abnormalities in the test groups as compared to the controls. The test and control groups (on the 90th day and the satellite group (on the 118th day were analyzed by measuring their final body and organ weights, taking necropsy, and examining hematology, blood clinical chemistry and histopathology. The results suggest that the water extract from the dried fruits of P. nigrum does not cause acute or subchronic toxicities in either male or female rats.

  1. Difficult Decisions: Animal Rights--Do We Have the Right to Do Research on Animals?

    Science.gov (United States)

    Parakh, Jal S.; Slesnick, Irwin L.

    1989-01-01

    Discusses who has the right to determine the use of animals in scientific research which includes medical experimentation and the toxicity testing of compounds, ranging from pesticides to cosmetics. Provides a list of questions for consideration and discussion. (RT)

  2. Enhancing the applicability and predictability of the embryonic stem cell test for developmental toxicity

    NARCIS (Netherlands)

    de Jong, E.

    2012-01-01

    Within the full risk assessment of a chemical, developmental toxicity testing is one of the endpoints that require the highest percentage of experimental animals. With the high number of experimental animals, cost and time involved in in vivo developmental toxicity testing there is an urgent need

  3. Repeated-dose toxicological studies of Tithonia diversifolia (Hemsl.) A. gray and identification of the toxic compounds.

    Science.gov (United States)

    Passoni, Flávia Donaire; Oliveira, Rejane Barbosa; Chagas-Paula, Daniela Aparecida; Gobbo-Neto, Leonardo; Da Costa, Fernando Batista

    2013-05-20

    Tithonia diversifolia (Hemsl.) A. Gray has been commonly used in folk medicine to treat abscesses, microbiological infections, snake bites, malaria and diabetes. Both anti-inflammatory and anti-malarial properties have been identified using appropriate assays, but the effective doses have demonstrated toxic effects for the experimental animals. Most of the pharmacological activities have been attributed to sesquiterpene lactones (STLs) and some chlorogenic acid derivatives (CAs) in the leaves of this species. This work aimed to evaluate the repeated-dose toxicity of an aqueous extract (AE) from Tithonia diversifolia leaves and to compare the results with an extract rich in STLs (LRE) and a polar extract (PE) without STLs but rich in CAs. The purpose of this work was to provide insights into the identity of the compounds responsible for the toxic effects of Tithonia diversifolia. The major classes of compounds were confirmed in each extract by IR spectra and HPLC-UV-DAD profiling using previously isolated or standard compounds. The toxicity of each extract was evaluated in a repeated-dose toxicity study in Wistar rats for 90 days. The AE is composed of both STLs and CAs, the LRE is rich in STLs, and the PE is rich in CAs. The AE caused alterations in haematological parameters but few alterations in biochemical parameters and was relatively safe at doses lower than 100mg/kg. However, the PE and LRE demonstrated several adverse effects by damaging the liver and kidneys, respectively. STLs and CAs can be toxic in prolonged use at higher doses in extracts prepared from Tithonia diversifolia by affecting the kidneys and liver. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Physical and biological dosimetry at the RA-3 facility for small animal irradiation: preliminary BNCT studies in an experimental model of oral cancer

    International Nuclear Information System (INIS)

    Pozzi, Emiliano; Miller, Marcelo; Thorp, Silvia I.; Heber, Elisa M.; Trivillin, Veronica A.; Zarza, Leandro; Estryk, Guillermo; Schwint, Amanda E.; Nigg, David W.

    2007-01-01

    Boron Neutron Capture Therapy (BNCT) is a binary treatment modality based on the capture reaction that occurs between thermal neutrons and boron-10 atoms that accumulate selectively in tumor tissue, emitting high linear energy transfer (LET), short range (5-9 microns) particles (alpha y 7 Li). Thus, BNCT would potentially target tumor tissue selectively, sparing normal tissue. Herein we evaluated the feasibility of treating experimental oral mucosa tumors with BNCT at RA-3 (CAE) employing the hamster cheek pouch oral cancer model and characterized the irradiation field at the RA-3 facility. We evaluated the therapeutic effect on tumor of BNCT mediated by BPA in the hamster cheek pouch oral cancer model and the potential radio toxic effects in normal tissue. We evidenced a moderate biological response in tumor, with no radio toxic effects in normal tissue following irradiations with no shielding for the animal body. Given the sub-optimal therapeutic response, we designed and built a 6 Li 2 CO 3 shielding for the body of the animal to increase the irradiation dose to tumor, without exceeding normal tissue radio tolerance. The measured absolute magnitude of thermal neutron flux and the characterization of the beam with and without the shielding in place, suggest that the irradiation facility in the thermal column of RA-3 would afford an excellent platform to perform BNCT studies in vitro and in vivo in small experimental animals. The present findings must be confirmed and extended by performing in vivo BNCT radiobiological studies in small experimental animals, employing the shielding device for the animal body. (author) [es

  5. Metal metabolism and toxicity

    International Nuclear Information System (INIS)

    Bhattacharyya, M.H.; Larsen, R.P.; Whelton, B.D.; Moretti, E.S.; Peterson, D.P.; Oldham, R.D.

    1985-01-01

    This research focuses on the role of pregnancy and lactation in susceptibility to the toxic effects of cadmium and lead. Responses under investigation include lead-induced changes in pathways for vitamin D and calcium metabolism and cadmium-induced alterations in kidney function and skeletal structure. The second area focuses on the gastrointestinal absorption of plutonium and other actinide elements. Studies currently being conducted in nonhuman primates to develop a procedure to determine GI absorption values of uranium and plutonium that does not require sacrifice of the animal. 6 refs

  6. INVESTIGATION OF ENROFLOXACIN-ASSOCIATED RETINAL TOXICITY IN NONDOMESTIC FELIDS.

    Science.gov (United States)

    Newkirk, Kim M; Beard, L Kathryn; Sun, Xiaocun; Ramsay, Edward C

    2017-06-01

    Enrofloxacin is known to cause retinal toxicity in domestic cats. The hallmark lesion of enrofloxacin-associated retinal toxicity in domestic cats is thinning of the outer nuclear layer of the retina. Enrofloxacin is commonly used to treat bacterial infections in nondomestic felids because of its action against a wide spectrum of bacteria and the ability for it to be given orally. No previous studies have investigated the potential retinal toxicity of enrofloxacin in nondomestic felids. This retrospective study evaluated 81 eyes from 14 lions ( Panthera leo ) and 33 tigers ( Panthera tigris ) that had been enucleated or collected postmortem. The thickness of the outer nuclear retina was assessed in two separate sites in each eye by counting the rows of nuclei and by using digital image analysis software to determine the area of the nuclei at each site. Medical records were reviewed to determine the enrofloxacin dose for each cat. Cats that had not received enrofloxacin (n = 11) were compared with treated animals (n = 36). The outer nuclear layer thickness or area in treated versus untreated cats was not significantly different. Additionally, no clinical blindness was reported in any of the cats. This study showed no evidence of enrofloxacin-associated thinning of the outer nuclear layer in the lions and tigers evaluated, suggesting that enrofloxacin can be used safely in these animals.

  7. The studies on the toxicity mechanism of environmentally hazardous natural (IAA) and synthetic (NAA) auxin--The experiments on model Arabidopsis thaliana and rat liver plasma membranes.

    Science.gov (United States)

    Hąc-Wydro, Katarzyna; Flasiński, Michał

    2015-06-01

    This paper concerns the studies towards membrane-damage effect of two auxins: indole-3-acetic acid - IAA and 1-naphthaleneacetic acid - NAA on plant (Arabidopsis thaliana) and animal (rat liver) model membranes. The foregoing auxins are plant growth regulators widely used in agriculture to control the quality of the crop. However, their accumulation in the environment makes them hazardous for the living organisms. The aim of our investigations was to compare the effect of natural (IAA) vs. synthetic (NAA) auxin on the organization of plant and animal model membranes and find a possible correlation between membrane-disturbing effect of these compounds and their toxicity. The collected data evidenced that auxins cause destabilization of membranes, decrease their condensation and weakens interactions of molecules. The alterations in the morphology of model systems were also noticed. The foregoing effects of auxins are concentration-dependent and additionally NAA was found to act on animal vs. plant membranes more selectively than IAA. Interestingly, both IAA and NAA induce the strongest disordering in model lipid system at the concentration, which is frequently reported as toxic to animal and plants. Based on the above findings it was proposed that membrane-damage effect induced by IAA and NAA may be important from the point of view of the mechanism of toxicity of these compounds and cannot be ignored in further investigations in this area. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Toxicity of inhaled alpha-emitting radionuclides - Status report

    Energy Technology Data Exchange (ETDEWEB)

    Muggenburg, B A; Mewhinney, J A; Guilmette, R A; Gillett, N A; Diel, J H; Lundgren, D L; Hahn, F F; Boecker, B B; McClellan, R O

    1988-12-01

    The toxicity of inhaled alpha-emitting radionuclides is being investigated in a series of interrelated dose-response studies. Dogs, rodents, and nonhuman primates have been exposed to monodisperse or polydisperse aerosols of the oxides of {sup 239}Pu, {sup 238}Pu, {sup 241}Am, or {sup 244}Cm to measure the relative importance of average organ dose, local dose around particles, specific activity, chemical form, particle size, and number of particles inhaled to the development of biological effects. The influence of animal species, age at exposure, and pre-existing lung disease, as well as the effects of repeated exposure, are also being studied, because they may influence the toxicity of these radionuclides. (author)

  9. Recommendations for Clinical Pathology Data Generation, Interpretation, and Reporting in Target Animal Safety Studies for Veterinary Drug Development.

    Science.gov (United States)

    Siska, William; Gupta, Aradhana; Tomlinson, Lindsay; Tripathi, Niraj; von Beust, Barbara

    Clinical pathology testing is routinely performed in target animal safety studies in order to identify potential toxicity associated with administration of an investigational veterinary pharmaceutical product. Regulatory and other testing guidelines that address such studies provide recommendations for clinical pathology testing but occasionally contain outdated analytes and do not take into account interspecies physiologic differences that affect the practical selection of appropriate clinical pathology tests. Additionally, strong emphasis is often placed on statistical analysis and use of reference intervals for interpretation of test article-related clinical pathology changes, with limited attention given to the critical scientific review of clinically, toxicologically, or biologically relevant changes. The purpose of this communication from the Regulatory Affairs Committee of the American Society for Veterinary Clinical Pathology is to provide current recommendations for clinical pathology testing and data interpretation in target animal safety studies and thereby enhance the value of clinical pathology testing in these studies.

  10. Toxicity attenuation optimization of crotalic venom by gamma radiation and studies of its immunogenic properties

    International Nuclear Information System (INIS)

    Clissa, Patricia Bianca

    1997-01-01

    Literature data show that 2.0 kGy dose of gamma radiation, generated by 60 source, reduces the toxic activity of Crotalus durissus terrificus venom, without altering its immunogenic capacity. When crotoxin, main toxin from crotalic venom, was irradiated with the same dose, toxicity was also reduced and the immunogenicity was maintained. This fact was attributed to aggregates (compounds with high molecular weight generated during irradiation), that showed no toxicity but were able to induce the antibodies formation against native venom. Crotalus durissus terrificus venom was irradiated with 2.0, 3.0, 5.0 and 10.0 kGy doses and submitted to molecular exclusion chromatography, in order to find an efficient dose that produces large amounts of non toxic but still immunogenic aggregates. After being isolated, the products of irradiation were evaluated for the amount produced, molecular alteration, and toxic and immunogenic activities. These parameters were also analyzed for the whole venom irradiated. The results from different doses irradiated venom were compared with native one, and 2.0 kGy dose was confirmed to be the most efficient in the association of toxicity attenuation with maintenance of immunogenicity of the crotalic venom, while other doses, in spite of being efficient in the toxicity attenuation, they were not able to keep the immunogenicity property. So, the dose of 2.0 kGy could be used to immunize animals in order to improve anticrotalic sera production. (author)

  11. Antihyperglycemic and subchronic toxicity study of Moringa stenopetala leaves in mice

    Directory of Open Access Journals (Sweden)

    Tesemma Sileshi

    2014-03-01

    Full Text Available Objective: To evaluate the antihyperglycemic activity and subchronic toxicity of an extract of Moringa stenopetala (M. stenopetala leaves in mice. Methods: Antihyperglycemic activities of various solvent subfractions and chromatographic fractions were investigated in alloxan induced diabetic mice. All fractions were administered intragastrically using oral gavage at a dose of 500 mg/kg. For the subchronic toxicity investigation of the 70% ethanol extract of M. stenopetala leaves, a daily dose of 300 or 600 mg/kg body weight was administered to mice over 96 d. Some hematological and plasma biochemical parameters were measured as indices of organ specific toxicity. Preliminary phytochemical screening and antioxidant activity investigation was done using thin layer chromatography method. Results: Among the solvent subfractions of the 70% ethanol extract tested only butanol subfraction exhibited significant reduction of blood glucose level (P<0.05 at 2 h (53.44% and 4.5 h (46.34% in diabetic mice and it was further fractionated chromatographically. This resulted in isolation of three chromatographic fractions (fraction 1, 2, and 3 which exhibited maximal blood glucose reduction (P<0.01 at 6 h (77.2%, at 4.5 h (69.1% and at 4.5 h (71.96% after administration. Furthermore, these fractions exhibited comparable antioxidant activity, and preliminary phytochemical screening indicated the presence of phenolic compounds which may be phenolic glycoside in all fractions. The subchronic toxicity study of the 70% ethanol extract of M. stenopetala leaves revealed that there were no significant differences in body weight, between controls and treated mice. Hematological analysis showed no differences in most parameters examined. Furthermore, it did not significantly affect plasma creatinine, urea, cholesterol, triglycerides and CA125 levels. It also did not significantly affect the plasma T3, T4 and THS level. It, however, caused a significant dose

  12. Neurobehavioral toxicity of cadmium sulfate to the planarian Dugesia dorotocephala

    Energy Technology Data Exchange (ETDEWEB)

    Grebe, E.; Schaeffer, D.J. (Univ. of Illinois, Urbana (United States))

    1991-05-01

    The authors are developing bioassays which use planarians (free-living platyhelminthes) for the rapid determination of various types of toxicity, including acute mortality, tumorigenicity, and short-term neurobehavioral responses. Their motivation for using these animals is due to their importance as components of the aquatic ecology of unpolluted streams their sensitivity to low concentrations of environmental toxicants and the presence of a sensitive neurological system with a true brain which allows for complex social behavior. A previous paper described the results of a neurobehavioral bioassay using phenol in a crossover study. This paper reports a similar crossover study using cadmium sulfate.

  13. Chemical toxicity and radioactivity of depleted uranium: The evidence from in vivo and in vitro studies.

    Science.gov (United States)

    Asic, Adna; Kurtovic-Kozaric, Amina; Besic, Larisa; Mehinovic, Lejla; Hasic, Azra; Kozaric, Mirza; Hukic, Mirsada; Marjanovic, Damir

    2017-07-01

    The main aim of this review is to summarize and discuss the current state of knowledge on chemical toxicity and radioactivity of depleted uranium (DU) and their effect on living systems and cell lines. This was done by presenting a summary of previous investigations conducted on different mammalian body systems and cell cultures in terms of potential changes caused by either chemical toxicity or radioactivity of DU. In addition, the authors aimed to point out the limitations of those studies and possible future directions. The majority of both in vitro and in vivo studies performed using animal models regarding possible effects caused by acute or chronic DU exposure has been reviewed. Furthermore, exposure time and dose, DU particle solubility, and uranium isotopes as factors affecting the extent of DU effects have been discussed. Special attention has been dedicated to chromosomal aberrations, DNA damage and DNA breaks, as well as micronuclei formation and epigenetic changes, as DU has recently been considered a possible causative factor of all these processes. Therefore, this approach might represent a novel area of study of DU-related irradiation effects on health. Since different studies offer contradictory results, the main aim of this review is to summarize and briefly discuss previously obtained results in order to identify the current opinion on DU toxicity and radioactivity effects in relation to exposure type and duration, as well as DU properties. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Pulmonary toxicity of nanomaterials: a critical comparison of published in vitro assays and in vivo inhalation or instillation studies.

    Science.gov (United States)

    Landsiedel, Robert; Sauer, Ursula G; Ma-Hock, Lan; Schnekenburger, Jürgen; Wiemann, Martin

    2014-11-01

    To date, guidance on how to incorporate in vitro assays into integrated approaches for testing and assessment of nanomaterials is unavailable. In addressing this shortage, this review compares data from in vitro studies to results from in vivo inhalation or intratracheal instillation studies. Globular nanomaterials (ion-shedding silver and zinc oxide, poorly soluble titanium dioxide and cerium dioxide, and partly soluble amorphous silicon dioxide) and nanomaterials with higher aspect ratios (multiwalled carbon nanotubes) were assessed focusing on the Organisation for Economic Co-Operation and Development (OECD) reference nanomaterials for these substances. If in vitro assays are performed with dosages that reflect effective in vivo dosages, the mechanisms of nanomaterial toxicity can be assessed. In early tiers of integrated approaches for testing and assessment, knowledge on mechanisms of toxicity serves to group nanomaterials thereby reducing the need for animal testing.

  15. Studies of radiation and chemical toxicity. Progress report

    International Nuclear Information System (INIS)

    1986-01-01

    Annual report for the Studies of Radiation and Chemical Toxicity Program at the University of Rochester is presented. Progress is reported on four projects: Neurobehavorial Toxicity of Organometallic Fuel Additives, Mechanisms of Permanent and Delayed Pathologic Effects of Ionizing Radiation, Solid State Radiation Chemistry of the DNA Backbone, and Pulmonary Biochemistry

  16. A Study on the Single-dose Oral Toxicity of Super Key in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Jinhee Kim

    2015-09-01

    Full Text Available Objectives: This study was performed to analyze the single-dose oral toxicity of the super key (processed sulfur. Methods: All experiments were conducted at Medvill, an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP regulations. In order to investigate the oral toxicity of super key We administered it orally to Sprague-Dawley (SD rats. The SD rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of super key 500 mg/kg, 1,000 mg/kg and 2,000 mg/kg were administered to the experimental groups, and a dose of normal saline solution, 10 mL/kg, was administered to the control group. We examined the survival rates, weights, clinical signs, gross findings and necropsy findings. This study was conducted under the approval of the Institutional Animal Ethics Committee. (Approval number: A01-14018. Results: No deaths or abnormalities occurred in any of the four groups. Although slight decreases in the weights of some female rats were noted, no significant changes in weights or differences in the gross findings between the control group and the experimental groups were observed. To check for abnormalities in organs, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs. Conclusion: The results of this research showed that administration of 500 ─ 2,000 mg/kg of super key did not cause any changes in the weights or in the results of necropsy examinations. Neither did it result in any mortalities. The above findings suggest that treatment with super key is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

  17. Test of the acute lethal toxicity of pollutants to marine fish and invertebrates

    International Nuclear Information System (INIS)

    1989-01-01

    This reference method describes the measurement of the acute lethal toxicity of pollutants to marine animals (fish and invertebrates) by a static (non-continuous flow) method. Procedures are given for the determination of the toxicity curve (survival time-concentration relationship) and for the estimation of median lethal concentrations (LC50). The method is suitable for use with fish and macro-invertebrate species. It is not suitable for planktonic organisms nor for determining the toxicity of oil, oil dispersants or other petroleum products. Those methods are described in Reference Methods Nos. 44 and 45, respectively. The test animals are exposed, in groups of approximately ten, to each of several concentrations of the pollutant. The animals are observed, at intervals, for several days, the test solutions being renewed regularly. A record is maintained of the survival times of individual animals exposed to each concentration of pollutant. The medial survival time of each group of animals is determined from a graphical plot of the raw data after a log-probability transformation. Median survival times and their confidence limits are plotted against concentrations of test substance to give a toxicity curve. Additionally, the same experimental data can be used to estimate the median lethal concentration (LC50) of the test substance to the animals after different periods of exposure. 3 refs, 5 figs, 3 tabs

  18. Study on toxicity mutation of crown-vetch induced by radiation

    International Nuclear Information System (INIS)

    Yi Huying; Yu Hongbin; Ma Jianzong

    1992-01-01

    The suckers of Germany crown-vetch were irradiated by 60 Co gamma ray and fast neutron. The toxicity mutation frequency and genetic stability of crown-vetch were studied. The various toxicity mutants were found in M 1 . Most of the toxicity mutants was unstable in M 2 , Stable mutant was very few (about 2.0-12.9%). β-nitropropionic acid in the low toxicity mutants selected was 31.7-39.8 mg/g. Genetic characteristics of low toxicity mutants were stable in M 3 -M 5

  19. The role of intestinal microbiota in development of irinotecan toxicity and in toxicity reduction through dietary fibres in rats.

    Directory of Open Access Journals (Sweden)

    Xiaoxi B Lin

    Full Text Available CPT-11 is a drug used as chemotherapy for colorectal cancer. CPT-11 causes toxic side-effects in patients. CPT-11 toxicity has been attributed to the activity of intestinal microbiota, however, intestinal microbiota may also have protective effects in CP!-11 chemotherapy. This study aimed to elucidate mechanisms through which microbiota and dietary fibres could modify host health. Rats bearing a Ward colon carcinoma were treated with a two-cycle CPT-11/5-fluorouracil therapy recapitulating clinical therapy of colorectal cancer. Animals were fed with a semi-purified diet or a semi-purified diet was supplemented with non-digestible carbohydrates (isomalto-oligosaccharides, resistant starch, fructo-oligosaccharides, or inulin in 3 independent experiments. Changes in intestinal microbiota, bacteria translocating to mesenteric lymphnodes, cecal GUD activity, and cecal SCFA production, and the intestinal concentration of CPT-11 and its metabolites were analysed. Non-digestible carbohydrates significantly influenced feed intake, body weight and other indicators of animal health. The identification of translocating bacteria and their quantification in cecal microbiota indicated that overgrowth of the intestine by opportunistic pathogens was not a major contributor to CPT-11 toxicity. Remarkably, fecal GUD activity positively correlated to body weight and feed intake but negatively correlated to cecal SN-38 concentrations and IL1-β. The reduction in CPT-11 toxicity by non-digestible carbohydrates did not correlate to stimulation of specific bacterial taxa. However, cecal butyrate concentrations and feed intake were highly correlated. The protective role of intestinal butyrate production was substantiated by a positive correlation of the host expression of MCT1 (monocarboxylate transporter 1 with body weight as well as a positive correlation of the abundance of bacterial butyryl-CoA gene with cecal butyrate concentrations. These correlations support the

  20. Food plant toxicants and safety - Risk assessment and regulation of inherent toxicants in plant foods

    DEFF Research Database (Denmark)

    Essers, A.J.A.; Alink, G.M.; Speijers, G.J.A.

    1998-01-01

    The ADI as a tool for risk management and regulation of food additives and pesticide residues is not readily applicable to inherent food plant toxicants: The margin between actual intake and potentially toxic levels is often small; application of the default uncertainty factors used to derive ADI...... values, particularly when extrapolating from animal data, would prohibit the utilisation of the food, which may have an overall beneficial health effect. Levels of inherent toxicants are difficult to control; their complete removal is not always wanted, due to their function for the plant or for human...... health. The health impact of the inherent toxicant is often modified by factors in the food, e.g. the bioavailability from the matrix and interaction with other inherent constituents. Risk-benefit analysis should be made for different consumption scenarios, without the use of uncertainty factors. Crucial...

  1. Sodium arsenite-induced reproductive toxicities in male Wistar rats ...

    African Journals Online (AJOL)

    Sodium arsenite-induced reproductive toxicities in male Wistar rats: role of Tridax procumbens leaf extract. ... Bulletin of Animal Health and Production in Africa ... In the present study, the effects of ethanol leaf extract of Tridax procumbens ... in Groups B to D as compared to Group A was significantly reduced (p<0.05).

  2. Toxicity levels to humans during acute exposure to hydrogen fluoride - An update

    International Nuclear Information System (INIS)

    Halton, D.M.

    1995-09-01

    In March 1993, the Atomic Energy Control Board (AECB) commissioned and update of a 1984 review on the acute toxicity of hydrogen fluoride (HF). The study places particular emphasis on the effects of inhalation of gaseous HF and is divided into two main parts: a literature review and a lethal concentration (LC) estimation. The literature review summarizes data under four categories: animal studies, controlled human studies, community exposure, and industrial exposure. Data in these areas were critically reviewed for their relevance to lethal concentrations at LC LO , LC 10 and LC 50 levels that were derived in the 1984 report. In the last ten years, only one relevant animal study has been published. No new controlled human studies were found but a community exposure incident was reported. There were three new industrial/accidental exposures reported since 1984. Evaluation of new data does not change the lethal concentration estimates made in the 1984 report, but does indicate the absence of appropriate models to estimate the lethality of irritant and corrosive gases. In the last 10 years, much literature on the evaluation of major hazards has been published and suggests that such assessments are of growing political, economic and social importance. Numerous articles have been published on the acute toxicity of HF from skin contact and chronic toxicity from repeated airborne exposure. These publications offer important insights into the nature of HF toxicity. Several avenues of investigative research are suggested. (author). 55 refs., 4 tabs

  3. Toxicity levels to humans during acute exposure to hydrogen fluoride - An update

    Energy Technology Data Exchange (ETDEWEB)

    Halton, D M

    1995-09-01

    In March 1993, the Atomic Energy Control Board (AECB) commissioned and update of a 1984 review on the acute toxicity of hydrogen fluoride (HF). The study places particular emphasis on the effects of inhalation of gaseous HF and is divided into two main parts: a literature review and a lethal concentration (LC) estimation. The literature review summarizes data under four categories: animal studies, controlled human studies, community exposure, and industrial exposure. Data in these areas were critically reviewed for their relevance to lethal concentrations at LC{sub LO}, LC{sub 10} and LC{sub 50} levels that were derived in the 1984 report. In the last ten years, only one relevant animal study has been published. No new controlled human studies were found but a community exposure incident was reported. There were three new industrial/accidental exposures reported since 1984. Evaluation of new data does not change the lethal concentration estimates made in the 1984 report, but does indicate the absence of appropriate models to estimate the lethality of irritant and corrosive gases. In the last 10 years, much literature on the evaluation of major hazards has been published and suggests that such assessments are of growing political, economic and social importance. Numerous articles have been published on the acute toxicity of HF from skin contact and chronic toxicity from repeated airborne exposure. These publications offer important insights into the nature of HF toxicity. Several avenues of investigative research are suggested. (author). 55 refs., 4 tabs.

  4. Paraquat: model for oxidant-initiated toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Bus, J.S.; Gibson, J.E.

    1984-04-01

    Paraquat, a quaternary ammonium bipyridyl herbicide, produces degenerative lesions in the lung after systemic administration to man and animals. The pulmonary toxicity of paraquat resembles in several ways the toxicity of several other lung toxins, including oxygen, nitrofurantoin and bleomycin. Although a definitive mechanism of toxicity of parquat has not been delineated, a cyclic single electron reduction/oxidation of the parent molecule is a critical mechanistic event. The redox cycling of paraquat has two potentially important consequences relevant to the development of toxicity: generation of activated oxygen (e.g., superoxide anion, hydrogen perioxide, hydroxyl radical) which is highly reactive to cellular macromolecules; and/or oxidation of reducing equivalents (e.g., NADPH, reduced glutathione) necessary for normal cell function. Paraquat-induced pulmonary toxicity, therefore, is a potentially useful model for evaluation of oxidant mechanisms of toxicity. Furthermore, characterization of the consequences of intracellular redox cycling of xenobiotics will no doubt provide basic information regarding the role of this phenomena in the development of chemical toxicity. 105 references, 2 figures.

  5. A study on toxicity of gasoline and GM-10 on liver of mice and it's amelioration by black tea extract.

    Science.gov (United States)

    Verma, Ramtej Jayram; Dave, Manjeet; Mathuria, Neeta

    2008-01-01

    The aim of present study is to investigate the ameliorative effect of black tea extract on gasoline and GM-10 induced toxicity in liver of mice. Eighty healthy male mice weighing 38-40 g approximately were divided into eight groups which included untreated control and various treated groups. Mice were treated with Gasoline 462 mg/kg/day and GM-10 low dose (206 mg/kg/day) and high dose (412 mg/kg/day) subcutaneously for 30 days. Black tea extract was given as 2 g/100 mL drinking water (2% w/v) instead of pure drinking water. All the animals were sacrificed on 31st day by cervical dislocation and livers were isolated and weighed. Parameters such as lipid peroxidation, catalase, superoxide dismutase, glutathione peroxidase, glutathione and total ascorbic acid were studied. The results revealed dose-dependent toxicity of gasoline and GM-10 on liver. Administration of black tea extract ameliorates this toxicity of gasoline and GM-10 in liver of mice. This proves the effective ameliorative effect of black tea extract.

  6. Acute and subacute toxicity of {sup 18F}-FDG

    Energy Technology Data Exchange (ETDEWEB)

    Dantas, Danielle M.; Silva, Natanael G. da; Manetta, Ana Paula; Osso Junior, Joao A., E-mail: danielle_2705@hotmail.com, E-mail: jaossoj@yahoo.com.br, E-mail: ngsilva@ipen.br, E-mail: apaulasp2008@hotmail.co [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Before initiating clinical trials of a new drug, it is necessary to perform a battery of safety tests, for evaluating the risk in humans. Radiopharmaceuticals must be tested taking into account its specificity, duration of treatment and especially the toxicity of both, the unlabelled molecule and its radionuclide, apart from impurities emanating from radiolysis. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when ANVISA established the Resolutions No. 63, which refers to the Good Manufacturing Practices of radiopharmaceuticals and No. 64 which seeks the registration of radiopharmaceuticals. Nowadays IPEN produces one of the most important radiopharmaceutical for nuclear medicine, the {sup 18}F-FDG, which is used in the diagnosis. The objective of this study is to assess systemic toxicity (acute / subacute) of {sup 18}F-FDG in an in vivo test system, as recommended by the RDC No. 64. In acute tests the administration occurred on the first day, healthy rats were observed for 14 days reporting their clinical signs and water consumption, and on the 15th day they were euthanized and necropsied. The assay of subacute toxicity observations were made over a period of 28 days and the first dose was administered at the beginning of the test and after a fortnight a second dose was administered. The parameters evaluated were the necropsy, histopathology of target organs, hematology studies and liver and kidney function. The results are being processed and evaluated. Initial observations did not show any acute toxicity in animals when compared to control animals. (author)

  7. Toxicity of tritium

    International Nuclear Information System (INIS)

    Dobson, R.L.

    1979-01-01

    Among radionuclides of importance in atomic energy, 3 H has relatively low toxicity. The main health and environmental worry is the possibility that significant biological effects may follow from protracted exposure to low concentrations in water. To examine this possible hazard and measure toxicity at low tritium concentrations, chronic exposure studies were done on mice and monkeys. During vulnerable developmental periods animals were exposed to 3 HOH, and mice were exposed also to 60 Co gamma irradiation and energy-related chemical agents. The biological endpoint measured was the irreversible loss of female germ cells. Effects from tritium were observed at surprisingly low concentrations where 3 H was found more damaging than previously thought. Comparisons between tritium and gamma radiation showed the relative biological effectiveness (RBE) to be greater than 1 and to reach approximately 3 at very low exposures. For perspective, other comparisons were made: between radiation and chemical agents, which revealed parallels in action on germ cells, and between pre- and postnatal exposure, which warn of possible special hazard to the fetus from both classes of energy-related byproducts

  8. Discriminating modes of toxic action in mice using toxicity in BALB/c mouse fibroblast (3T3) cells.

    Science.gov (United States)

    Huang, Tao; Yan, Lichen; Zheng, Shanshan; Wang, Yue; Wang, Xiaohong; Fan, Lingyun; Li, Chao; Zhao, Yuanhui; Martyniuk, Christopher J

    2017-12-01

    The objective of this study was to determine whether toxicity in mouse fibroblast cells (3T3 cells) could predict toxicity in mice. Synthesized data on toxicity was subjected to regression analysis and it was observed that relationship of toxicities between mice and 3T3 cells was not strong (R 2  = 0.41). Inclusion of molecular descriptors (e.g. ionization, pKa) improved the regression to R 2  = 0.56, indicating that this relationship is influenced by kinetic processes of chemicals or specific toxic mechanisms associated to the compounds. However, to determine if we were able to discriminate modes of action (MOAs) in mice using the toxicities generated from 3T3 cells, compounds were first classified into "baseline" and "reactive" guided by the toxic ratio (TR) for each compound in mice. Sequence, binomial and recursive partitioning analyses provided strong predictions of MOAs in mice based upon toxicities in 3T3 cells. The correct classification of MOAs based on these methods was 86%. Nearly all the baseline compounds predicted from toxicities in 3T3 cells were identified as baseline compounds from the TR in mice. The incorrect assignment of MOAs for some compounds is hypothesized to be due to experimental uncertainty that exists in toxicity assays for both mice and 3T3 cells. Conversely, lack of assignment can also arise because some reactive compounds have MOAs that are different in mice compared to 3T3 cells. The methods developed here are novel and contribute to efforts to reduce animal numbers in toxicity tests that are used to evaluate risks associated with organic pollutants in the environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Test systems to identify reproductive toxicants.

    Science.gov (United States)

    Riecke, K; Stahlmann, R

    2000-09-01

    Experience with drugs and other xenobiotics indicates that both animal testing and epidemiological studies are necessary to provide adequate data for an estimation of risks that might be associated with exposure to a chemical substance. In this review, the pros and cons of test systems for reproductive toxicity are discussed. Usually, several studies are performed to cover the different phases of the reproductive cycle. In the preclinical development of drugs, the three so-called 'segment testing protocols' have been used for several decades now. More recently, new testing concepts have been accepted internationally which include more flexibility in implementation. Several examples of compounds with the potential for reproductive toxicity are presented in more detail in a discussion of some pitfalls of the tests for fertility (phthalates and fluoroquinolones), teratogenicity (acyclovir and protease inhibitors) and postnatal developmental toxicity (fluoroquinolones). In addition, important aspects of kinetics and metabolism as a prerequisite for a rational interpretation of results from toxicological studies are briefly discussed. In vitro assays are useful for supplementing the routinely used in vivo approaches or for studying an expected or defined effect, but they are not suitable for revealing an unknown effect of a chemical on the complex reproductive process.

  10. Haloacetonitriles: metabolism and toxicity.

    Science.gov (United States)

    Lipscomb, John C; El-Demerdash, Ebtehal; Ahmed, Ahmed E

    2009-01-01

    bioactivation process, depending on the particular HAN and the enzyme involved. HANs can inhibit CYP2E1-mediated metabolism, an effect which may be dependent on a covalent interaction with the enzyme. In addition, HAN compounds inhibit GST-mediated conjugation, but this effect is reversible upon dialysis, indicating that the interaction does not represent covalent binding. No subchronic studies of HAN toxicity are available in the literature. However, studies show that HANs produce developmental toxicity in experimental animals. The nature of developmental toxicity is affected by the type of administration vehicle, which renders interpretation of results more difficult. Skin tumors have been found following dermal application of HANs, but oral studies for carcinogenicity are negative. Pulmonary adenomas were increased following oral administration of HANs, but the A/J strain of mice employed has a characteristically high background rate of such tumors. HANs interact with DNA to produce unscheduled DNA repair, SCE and reverse mutations in Salmonella. HANs did not induce micronuclei or cause alterations in sperm head morphology in mice, but did induce micronuclei in newts. Thus, there is concern for the potential carcinogenicity of HANs. It would be valuable to delineate any relationship between the apparent threshold for micronuclei formation in newts and the potential mechanism of toxicity involving HAN-induced oxidative stress. Dose-response studies in rodents may provide useful information on toxicity mechanisms and dose selection for longer term toxicity studies. Additional studies are warranted before drawing firm conclusions on the hazards of HAN exposure. Moreover, additional studies on HAN-DNA and HAN-protein interaction mechanisms, are needed. Such studies can better characterize the role of metabolism in toxicity of individual HANs, and delineate the role of oxidative stress, both of which enhance the capacity to predict risk. Most needed, now, are new subchronic (and

  11. Acute toxicity study of Vilocym Premix (herbal growth promoter for Livestockin Wistar Albino Rat

    Directory of Open Access Journals (Sweden)

    A.H. Ahmad

    2009-06-01

    Full Text Available An experimental study with the objective of safety evaluation of Vilocym Premix, herbal growth promoter for Livestock (supplied by Ayurvet Ltd., Baddi, India, was done as per standard guidelines of OECD-423 for acute toxicity testing. Vilocym Premix is a scientifically developed combination of herbs that contains herbal ingredients namely Azadirachta indica, Curcuma longa & many more alongwith natural zeolites. The study was done in 3 males and 3 female Wistar Albino rats, which were administered an initial dose of 50 mg/kg body weight followed by dose rates of 300, 500 & 5000 mg/kg body weight of test compound. The animals were observed for signs of convulsions, tremors, circling, depression, excitement and mortality. Body weight was recorded at 0,7th and 14th day and plasma total protein, albumin; AST and ALT were measured after 3rd day of experiment. No abnormal sign of symptoms were observed in any of the animal fed with Vilocym Premix at the dose rate of 50, 300, 500 & 5000 mg/kg. No mortality was observed indicating safety of herbal premix. [Vet. World 2009; 2(3.000: 100-102

  12. TOXICITY TESTING IN THE 21ST CENTURY: A VISION AND A STRATEGY

    DEFF Research Database (Denmark)

    Krewski, D.; Acosta, D.; Andersen, M.

    2010-01-01

    With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U. S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal ...

  13. Acute, reproductive toxicity and two-generation teratology studies of a standardized quassinoid-rich extract of Eurycoma longifolia Jack in Sprague-Dawley rats.

    Science.gov (United States)

    Low, Bin-Seng; Das, Prashanta Kumar; Chan, Kit-Lam

    2014-07-01

    The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Transport phenomena of nanoparticles in plants and animals/humans.

    Science.gov (United States)

    Anjum, Naser A; Rodrigo, Miguel Angel Merlos; Moulick, Amitava; Heger, Zbynek; Kopel, Pavel; Zítka, Ondřej; Adam, Vojtech; Lukatkin, Alexander S; Duarte, Armando C; Pereira, Eduarda; Kizek, Rene

    2016-11-01

    The interaction of a plethora nanoparticles with major biota such as plants and animals/humans has been the subject of various multidisciplinary studies with special emphasis on toxicity aspects. However, reports are meager on the transport phenomena of nanoparticles in the plant-animal/human system. Since plants and animals/humans are closely linked via food chain, discussion is imperative on the main processes and mechanisms underlying the transport phenomena of nanoparticles in the plant-animal/human system, which is the main objective of this paper. Based on the literature appraised herein, it is recommended to perform an exhaustive exploration of so far least explored aspects such as reproducibility, predictability, and compliance risks of nanoparticles, and insights into underlying mechanisms in context with their transport phenomenon in the plant-animal/human system. The outcomes of the suggested studies can provide important clues for fetching significant benefits of rapidly expanding nanotechnology to the plant-animal/human health-improvements and protection as well. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. The discovery and development of proteomic safety biomarkers for the detection of drug-induced liver toxicity

    International Nuclear Information System (INIS)

    Amacher, David E.

    2010-01-01

    Biomarkers are biometric measurements that provide critical quantitative information about the biological condition of the animal or individual being tested. In drug safety studies, established toxicity biomarkers are used along with other conventional study data to determine dose-limiting organ toxicity, and to define species sensitivity for new chemical entities intended for possible use as human medicines. A continuing goal of drug safety scientists in the pharmaceutical industry is to discover and develop better trans-species biomarkers that can be used to determine target organ toxicities for preclinical species in short-term studies at dose levels that are some multiple of the intended human dose and again later in full development for monitoring clinical trials at lower therapeutic doses. Of particular value are early, predictive, noninvasive biomarkers that have in vitro, in vivo, and clinical transferability. Such translational biomarkers bridge animal testing used in preclinical science and human studies that are part of subsequent clinical testing. Although suitable for in vivo preclinical regulatory studies, conventional hepatic safety biomarkers are basically confirmatory markers because they signal organ toxicity after some pathological damage has occurred, and are therefore not well-suited for short-term, predictive screening assays early in the discovery-to-development progression of new chemical entities (NCEs) available in limited quantities. Efforts between regulatory agencies and the pharmaceutical industry are underway for the coordinated discovery, qualification, verification and validation of early predictive toxicity biomarkers. Early predictive safety biomarkers are those that are detectable and quantifiable prior to the onset of irreversible tissue injury and which are associated with a mechanism of action relevant to a specific type of potential hepatic injury. Potential drug toxicity biomarkers are typically endogenous macromolecules in

  16. Effects of nanotoxicity on female reproductivity and fetal development in animal models.

    Science.gov (United States)

    Sun, Jianling; Zhang, Qiu; Wang, Zhiping; Yan, Bing

    2013-04-29

    The extensive application of nanomaterials in industry, medicine and consumer products has raised concerns about their potential toxicity. The female population is particularly vulnerable and deserves special attention because toxicity in this group may impact both female reproductivity and fetal development. Mouse and zebrafish models each have their own unique features and studies using these models to examine the potential toxicity of various nanoparticles are compared and summarized in this review. Several nanoparticles exhibit detrimental effects on female reproductivity as well as fetal development, and these adverse effects are related to nanoparticle composition, surface modification, dose, exposure route and animal species. Limited studies on the mechanisms of nanotoxicity are also documented and reviewed herein.

  17. Effects of Nanotoxicity on Female Reproductivity and Fetal Development in Animal Models

    Directory of Open Access Journals (Sweden)

    Jianling Sun

    2013-04-01

    Full Text Available The extensive application of nanomaterials in industry, medicine and consumer products has raised concerns about their potential toxicity. The female population is particularly vulnerable and deserves special attention because toxicity in this group may impact both female reproductivity and fetal development. Mouse and zebrafish models each have their own unique features and studies using these models to examine the potential toxicity of various nanoparticles are compared and summarized in this review. Several nanoparticles exhibit detrimental effects on female reproductivity as well as fetal development, and these adverse effects are related to nanoparticle composition, surface modification, dose, exposure route and animal species. Limited studies on the mechanisms of nanotoxicity are also documented and reviewed herein.

  18. Methods of acute biological assays in guinea-pigs for the study of toxicity and innocuity of drugs and chemicals

    Directory of Open Access Journals (Sweden)

    Gui Mi Ko

    2010-06-01

    Full Text Available In this study, 602 samples were tested by the following assays performed at the animal facilities (Cedeme of the Federal University of São Paulo (UNIFESP: 385 for dermal irritability, 90 for ocular irritability (discontinued in 1995, 31 for systemic toxicity by injection, 26 for oral acute toxicity, 15 for toxicity by intracutaneous injection, 15 for skin sensitization, 15 for toxicity of serum and vaccines for human use, 14 for toxicity by intramuscular implantation, 7 for pyrogens, 2 for acute dermal toxicity, and 2 for irritation of mucous membrane. The following agents were tested: cosmetics and related substances (42.0%, chemicals used in industry (32.9%, plastics, rubber, and other polymers (15.9%, agrotoxics (4.0%, medicines (2.7%, and vaccines (2.5%. In the present description, emphasis was given to tests of dermal irritability and sensitization. This work was conducted entirely in animal facilities, according to our general belief that animal facilities at universities, while considering ethic principles and sanitary, genetic, nutritional, and pathophysiological controls, also require laboratories specialized in areas such as transgenics, cryopreservation, ambiental physiology, functional genomics, alternative models, and mainly activities and research on methods in toxicology, as focused in this study.Descrevemos os testes usados em ensaios biológicos de curta duração para estudo de toxicidade e inocuidade de cosméticos, fármacos e outras substâncias químicas, feitos no Biotério Central/Cedeme da Unifesp, de 1986 a 2000. Testamos 602 amostras nos seguintes ensaios: 385 de irritação cutânea, 90 de irritação ocular (até 1995, 31 de toxicidade sistêmica por injeção, 26 de toxicidade oral aguda, 15 de toxicidade por aplicação intracutânea, 15 de sensibilização da pele, 15 de toxicidade de soros e vacinas de uso humano, 14 de toxicidade por implantação intramuscular, 7 de pirogênio, 2 de toxicidade dérmica aguda e

  19. An Empirical Study Analyzing Job Productivity in Toxic Workplace Environments.

    Science.gov (United States)

    Anjum, Amna; Ming, Xu; Siddiqi, Ahmed Faisal; Rasool, Samma Faiz

    2018-05-21

    Purpose: This empirical study aims to determine the effects of a toxic workplace environment, which can negatively impact the job productivity of an employee. Methodology: Three hundred questionnaires were randomly distributed among the staff members of seven private universities in Pakistan with a final response rate of 89%. For analysis purposes, AMOS 22 was used to study the direct and indirect effects of the toxic workplace environment on job productivity. Confirmatory Factor Analysis (CFA) was conducted to ensure the convergent and discriminant validity of the factors, while the Hayes mediation approach was used to verify the mediating role of job burnout between the four dimensions of toxic workplace environment and job productivity. A toxic workplace with multiple dimensions, such as workplace ostracism, workplace incivility, workplace harassment, and workplace bullying, was used in this study. Findings: By using the multiple statistical tools and techniques, it has been proven that ostracism, incivility, harassment, and bullying have direct negative significant effects on job productivity, while job burnout was shown to be a statistical significant mediator between the dimensions of a toxic workplace environment and job productivity. Finally, we concluded that organizations need to eradicate the factors of toxic workplace environments to ensure their prosperity and success. Practical Implications: This study encourages managers, leaders, and top management to adopt appropriate policies for enhancing employees’ productivity. Limitations: This study was conducted by using a cross-sectional research design. Future research aims to expand the study by using a longitudinal research design.

  20. Enhancement of developmental toxicity effects of chemicals by gestational stress. A review

    DEFF Research Database (Denmark)

    Hougaard, Karin S; Hansen, Åse Marie

    2007-01-01

    Risk assessment of developmental toxicants is almost exclusively based on single chemicals studied in animals under controlled experimental conditions, as to reduce stress. Although humans may be exposed simultaneously to numerous hazards, little is known about the interaction of prenatal chemica...

  1. Study of the oocyte degenerescence at mouse: role of the caspases and toxicity of natural uranium

    International Nuclear Information System (INIS)

    Arnault, E.

    2008-04-01

    The aim of this work is to estimate the uranium toxicity on the ovarian function and on the oocyte and more fundamentally to characterize the molecular ways regulating the oocyte degenerescence. At first, will be described the different exposure modes at uranium and the known toxic effects of this heavy metal on man and animal. The mechanisms regulating the follicle genesis and the oogenesis are then developed. At last, will be given the data available in literature and concerning the apoptosis ways intervening in the follicular atresia and in the oocyte degenerescence while referring to the known ways of the somatic cells. (O.M.)

  2. 177Lu-DOTA-HH1, a novel anti-CD37 radio-immunoconjugate: a study of toxicity in nude mice.

    Directory of Open Access Journals (Sweden)

    Ada H V Repetto-Llamazares

    Full Text Available CD37 is an internalizing B-cell antigen expressed on Non-Hodgkin lymphoma (NHL and chronic lymphocytic leukemia cells (CLL. The anti-CD37 monoclonal antibody HH1 was conjugated to the bifunctional chelator p-SCN-Bn-DOTA and labelled with the beta-particle emitting radionuclide 177Lu creating the radio-immunoconjugate (RIC 177Lu-DOTA-HH1 (177Lu-HH1, trade name Betalutin. The present toxicity study was performed prior to initiation of clinical studies with 177Lu-HH1.Nude mice with or without tumor xenografts were treated with 50 to 1000 MBq/kg 177Lu- HH1 and followed for clinical signs of toxicity up to ten months. Acute, life threatening bone marrow toxicity was observed in animals receiving 800 and 1000 MBq/kg 177Lu-HH1. Significant changes in serum concentrations of liver enzymes were evident for treatment with 1000 MBq/kg 177Lu-HH1. Lymphoid depletion, liver necrosis and atrophy, and interstitial cell hyperplasia of the ovaries were also observed for mice in this dose group.177Lu-DOTA-HH1 was well tolerated at dosages about 10 times above those considered relevant for radioimmunotherapy in patients with B-cell derived malignancies.The toxicity profile was as expected for RICs. Our experimental results have paved the way for clinical evaluation of 177Lu-HH1 in NHL patients.

  3. Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model

    Directory of Open Access Journals (Sweden)

    Heshu Sulaiman Rahman

    2014-01-01

    Full Text Available Zerumbone- (ZER- loaded nanostructure lipid carrier (NLC (ZER-NLC prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50 of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration.

  4. A review of reproductive toxicity of microcystins

    International Nuclear Information System (INIS)

    Chen, Liang; Chen, Jun; Zhang, Xuezhen; Xie, Ping

    2016-01-01

    Highlights: • Reproductive toxicity of MCs on mammals, fishes, amphibians, and birds is reviewed. • PP1/2A inhibition and oxidative stress are important toxic mechanisms of MCs. • Reproductive toxicity of MCs may be closely related to endocrine-disrupting effects. • The trans-generational toxicity of microcystins is a matter of concern. • Data concerning female reproductive and sex-specific effects of MCs are lacking. - Abstract: Animal studies provide strong evidence of positive associations between microcystins (MCs) exposure and reproductive toxicity, representing a threat to human reproductive health and the biodiversity of wild life. This paper reviews current knowledge of the reproductive toxicity of MCs, with regard to mammals, fishes, amphibians, and birds, mostly in males. Toxicity of MCs is primarily governed by the inhibition of protein phosphatases 1 and 2A (PP1 and PP2A) and disturbance of cellular phosphorylation balance. MCs exposure is related to excessive production of reactive oxygen species (ROS) and oxidative stress, leading to cytoskeleton disruption, mitochondria dysfunction, endoplasmic reticulum (ER) stress, and DNA damage. MCs induce cell apoptosis mediated by the mitochondrial and ROS and ER pathways. Through PP1/2A inhibition and oxidative stress, MCs lead to differential expression/activity of transcriptional factors and proteins involved in the pathways of cellular differentiation, proliferation, and tumor promotion. MC-induced DNA damage is also involved in carcinogenicity. Apart from a direct effect on testes and ovaries, MCs indirectly affect sex hormones by damaging the hypothalamic-pituitary-gonad (HPG) axis and liver. Parental exposure to MCs may result in hepatotoxicity and neurotoxicity of offspring. We also summarize the current research gaps which should be addressed by further studies.

  5. A review of reproductive toxicity of microcystins

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Liang, E-mail: chan91@yeah.net [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Chen, Jun, E-mail: chenjun@ihb.ac.cn [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Zhang, Xuezhen, E-mail: xuezhen@mail.hzau.edu.cn [College of Fisheries, Huazhong Agricultural University, Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070 (China); Xie, Ping, E-mail: xieping@ihb.ac.cn [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China)

    2016-01-15

    Highlights: • Reproductive toxicity of MCs on mammals, fishes, amphibians, and birds is reviewed. • PP1/2A inhibition and oxidative stress are important toxic mechanisms of MCs. • Reproductive toxicity of MCs may be closely related to endocrine-disrupting effects. • The trans-generational toxicity of microcystins is a matter of concern. • Data concerning female reproductive and sex-specific effects of MCs are lacking. - Abstract: Animal studies provide strong evidence of positive associations between microcystins (MCs) exposure and reproductive toxicity, representing a threat to human reproductive health and the biodiversity of wild life. This paper reviews current knowledge of the reproductive toxicity of MCs, with regard to mammals, fishes, amphibians, and birds, mostly in males. Toxicity of MCs is primarily governed by the inhibition of protein phosphatases 1 and 2A (PP1 and PP2A) and disturbance of cellular phosphorylation balance. MCs exposure is related to excessive production of reactive oxygen species (ROS) and oxidative stress, leading to cytoskeleton disruption, mitochondria dysfunction, endoplasmic reticulum (ER) stress, and DNA damage. MCs induce cell apoptosis mediated by the mitochondrial and ROS and ER pathways. Through PP1/2A inhibition and oxidative stress, MCs lead to differential expression/activity of transcriptional factors and proteins involved in the pathways of cellular differentiation, proliferation, and tumor promotion. MC-induced DNA damage is also involved in carcinogenicity. Apart from a direct effect on testes and ovaries, MCs indirectly affect sex hormones by damaging the hypothalamic-pituitary-gonad (HPG) axis and liver. Parental exposure to MCs may result in hepatotoxicity and neurotoxicity of offspring. We also summarize the current research gaps which should be addressed by further studies.

  6. Alternatives to Animal Use in Research, Testing, and Education. Summary.

    Science.gov (United States)

    Congress of the U.S., Washington, DC. Office of Technology Assessment.

    With an estimated 17-22 million animals used in laboratories annually in the United States, public interest in animal welfare has sparked an often emotional debate over such uses of animals. Concerns focus on balancing societal needs for continued progress in biomedical and behavioral research, for toxicity testing to safeguard the public, and for…

  7. Treatment of textile effluent in a developed phytoreactor with immobilized bacterial augmentation and subsequent toxicity studies on Etheostoma olmstedi fish

    Energy Technology Data Exchange (ETDEWEB)

    Watharkar, Anuprita D. [Department of Biotechnology, Shivaji University, Kolhapur (India); Khandare, Rahul V. [School of Life Sciences, North Maharashtra University, Jalgaon (India); Waghmare, Pankajkumar R.; Jagadale, Ashwini D.; Govindwar, Sanjay P. [Department of Biochemistry, Shivaji University, Kolhapur (India); Jadhav, Jyoti P., E-mail: jpj_biochem@unishivaji.ac.in [Department of Biotechnology, Shivaji University, Kolhapur (India); Department of Biochemistry, Shivaji University, Kolhapur (India)

    2015-02-11

    Graphical abstract: - Highlights: • A phytoreactor was developed and augmented with immobilized bacteria. • This consortium showed enhanced treatment than the individual species. • Oxido-reductases from P. crinitum and B. pumilus could decolorize the effluent. • Characterization of effluent samples endorsed the efficacy of consortial strategy. • Toxicity studies revealed the less toxic nature of the consortium treated effluent. - Abstract: A static hydroponic bioreactor using nursery grown plants of Pogonatherum crinitum along with immobilized Bacillus pumilus cells was developed for the treatment of textile wastewater. Independent reactors with plants and immobilized cells were also kept for performance and efficacy evaluation. The effluent samples characterized before and after their treatment showed that the plant–bacterial consortium reactor was more efficient than those of individual plant and bacterium reactors. COD, BOD, ADMI, conductivity, turbidity, TDS and TSS of the textile effluent was found to be reduced by 78, 70, 93, 4, 90, 13 and 70% respectively within 12 d by the consortial set. HPTLC analysis revealed the transformation of the textile effluent to new products. The phytotoxicity study on Phaeseolus mungo and Sorghum vulgare seeds showed reduced toxicity of treated effluents. The animal toxicity study performed on Etheostoma olmstedi fishes showed the toxic nature of untreated effluent giving extreme stress to fishes leading to death. Histology of fish gills exposed to treated effluent was found to be less affected. The oxidative stress related enzymes like superoxide dismutase and catalase were found to show decreased activities and less lipid peroxidation in fishes exposed to treated effluent.

  8. Treatment of textile effluent in a developed phytoreactor with immobilized bacterial augmentation and subsequent toxicity studies on Etheostoma olmstedi fish

    International Nuclear Information System (INIS)

    Watharkar, Anuprita D.; Khandare, Rahul V.; Waghmare, Pankajkumar R.; Jagadale, Ashwini D.; Govindwar, Sanjay P.; Jadhav, Jyoti P.

    2015-01-01

    Graphical abstract: - Highlights: • A phytoreactor was developed and augmented with immobilized bacteria. • This consortium showed enhanced treatment than the individual species. • Oxido-reductases from P. crinitum and B. pumilus could decolorize the effluent. • Characterization of effluent samples endorsed the efficacy of consortial strategy. • Toxicity studies revealed the less toxic nature of the consortium treated effluent. - Abstract: A static hydroponic bioreactor using nursery grown plants of Pogonatherum crinitum along with immobilized Bacillus pumilus cells was developed for the treatment of textile wastewater. Independent reactors with plants and immobilized cells were also kept for performance and efficacy evaluation. The effluent samples characterized before and after their treatment showed that the plant–bacterial consortium reactor was more efficient than those of individual plant and bacterium reactors. COD, BOD, ADMI, conductivity, turbidity, TDS and TSS of the textile effluent was found to be reduced by 78, 70, 93, 4, 90, 13 and 70% respectively within 12 d by the consortial set. HPTLC analysis revealed the transformation of the textile effluent to new products. The phytotoxicity study on Phaeseolus mungo and Sorghum vulgare seeds showed reduced toxicity of treated effluents. The animal toxicity study performed on Etheostoma olmstedi fishes showed the toxic nature of untreated effluent giving extreme stress to fishes leading to death. Histology of fish gills exposed to treated effluent was found to be less affected. The oxidative stress related enzymes like superoxide dismutase and catalase were found to show decreased activities and less lipid peroxidation in fishes exposed to treated effluent

  9. Insights on in vitro models for safety and toxicity assessment of cosmetic ingredients.

    Science.gov (United States)

    Almeida, Andreia; Sarmento, Bruno; Rodrigues, Francisca

    2017-03-15

    According to the current European legislation, the safety assessment of each individual cosmetic ingredient of any formulation is the basis for the safety evaluation of a cosmetic product. Also, animal testing in the European Union is prohibited for cosmetic ingredients and products since 2004 and 2009, respectively. Additionally, the commercialization of any cosmetic products containing ingredients tested on animal models was forbidden in 2009. In consequence of these boundaries, the European Centre for the Validation of Alternative Methods (ECVAM) proposes a list of validated cell-based in vitro models for predicting the safety and toxicity of cosmetic ingredients. These models have been demonstrated as valuable and effective tools to overcome the limitations of animal in vivo studies. Although the use of in vitro cell-based models for the evaluation of absorption and permeability of cosmetic ingredients is widespread, a detailed study on the properties of these platforms and the in vitro-in vivo correlation compared with human data are required. Moreover, additional efforts must be taken to develop in vitro models to predict carcinogenicity, repeat dose toxicity and reproductive toxicity, for which no alternative in vitro methods are currently available. This review paper summarizes and characterizes the most relevant in vitro models validated by ECVAM employed to predict the safety and toxicology of cosmetic ingredients. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Studies on the toxicity of RSU-1069

    International Nuclear Information System (INIS)

    Whitmore, G.F.; Gulyas, S.

    1986-01-01

    RSU-1069 combines an aziridine function with a 2-nitroimidazole and has been reported to exhibit extraordinary radiosensitization both in vitro and in vivo. Such sensitization appears to be at variance with the electron affinity of the compound. In addition, recent experiments suggest that the compound is highly toxic to hypoxic tumor cells in vivo. On the assumption that the observed radiosensitizing ability may be a manifestation of toxicity and because of the high in vivo toxicity, we have investigated aerobic and hypoxic toxicity, both in wild type CHO cells and in mutants sensitive to a variety of DNA damaging agents. With wild type cells under aerobic conditions, the compound is approximately 50 times as toxic as misonidazole and under hypoxic conditions, approximately 250 times as toxic. The ratio of hypoxic to aerobic toxicity is approximately 80 times. Under aerobic conditions, repair-deficient mutants are 10 times as sensitive to RSU-1069 as wild type cells and approximately 100 times as sensitive under hypoxic conditions. The ratio of hypoxic to aerobic toxicity for the mutant cells is approximately 900. Based on these observations, we suggest that under aerobic conditions the aziridine function is primarily responsible for toxicity, whereas, under hypoxic conditions, the aziridine moiety combined with a reduced 2-nitroimidazole moiety produces a bifunctional agent

  11. Toxicity studies of six types of carbon nanoparticles in a chicken-embryo model

    Directory of Open Access Journals (Sweden)

    Kurantowicz N

    2017-04-01

    Full Text Available Natalia Kurantowicz,1 Ewa Sawosz,1 Gabriela Halik,1 Barbara Strojny,1 Anna Hotowy,1 Marta Grodzik,1 Radosław Piast,2 Wanvimol Pasanphan,3 André Chwalibog4 1Department of Animal Nutrition and Biotechnology, Warsaw University of Life Sciences, 2Faculty of Chemistry, Warsaw University, Warsaw, Poland; 3Department of Materials Science, Faculty of Science, Kasetsart University, Bangkok, Thailand; 4Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Copenhagen, Denmark Abstract: In the present study, the toxicity of six different types of carbon nanoparticles (CNPs was investigated using a chicken-embryo model. Fertilized chicken eggs were divided into the following treatment groups: placebo, diamond NPs, graphite NPs, pristine graphene, small graphene oxide, large graphene oxide, and reduced graphene oxide. Experimental solutions at a concentration of 500 µg/mL were administrated into the egg albumin. Gross pathology and the rate of survival were examined after 5, 10, 15, and 20 days of incubation. After 20 days of incubation, blood samples were collected and the weight of the body and organs measured. The relative ratio of embryo survival decreased after treatment all treatments except diamond NPs. There was no correlation between the rate of survival and the ζ-potential or the surface charge of the CNPs in solution. Body and organ weight, red blood-cell morphology, blood serum biochemical parameters, and oxidative damage in the liver did not differ among the groups. These results indicate that CNPs can remain in blood circulation without any major side effects, suggesting their potential applicability as vehicles for drug delivery or active compounds per se. However, there is a need for further investigation of their properties, which vary depending on production methods and surface functionalization. Keywords: nanoparticles, diamond, graphite, graphene, toxicity, red blood cells, oxidative stress, surface charge

  12. Dose-dependent transitions in mechanisms of toxicity: case studies

    International Nuclear Information System (INIS)

    Slikker, William; Andersen, Melvin E.; Bogdanffy, Matthew S.; Bus, James S.; Cohen, Steven D.; Conolly, Rory B.; David, Raymond M.; Doerrer, Nancy G.; Dorman, David C.; Gaylor, David W.; Hattis, Dale; Rogers, John M.; Setzer, R. Woodrow; Swenberg, James A.; Wallace, Kendall

    2004-01-01

    Experience with dose response and mechanisms of toxicity has shown that multiple mechanisms may exist for a single agent along the continuum of the full dose-response curve. It is highly likely that critical, limiting steps in any given mechanistic pathway may become overwhelmed with increasing exposures, signaling the emergence of new modalities of toxic tissue injury at these higher doses. Therefore, dose-dependent transitions in principal mechanisms of toxicity may occur, and could have significant impact on the interpretation of reference data sets for risk assessment. To illustrate the existence of dose-dependent transitions in mechanisms of toxicity, a group of academic, government, and industry scientists, formed under the leadership of the ILSI Health and Environmental Sciences Institute (HESI), developed a series of case studies. These case studies included acetaminophen, butadiene, ethylene glycol, formaldehyde, manganese, methylene chloride, peroxisome proliferator-activated receptor (PPAR), progesterone/hydroxyflutamide, propylene oxide, vinyl acetate, vinyl chloride, vinylidene chloride, and zinc. The case studies formed the basis for technical discourse at two scientific workshops in 2003

  13. Alternatives to animal testing: research, trends, validation, regulatory acceptance.

    Science.gov (United States)

    Huggins, Jane

    2003-01-01

    Current trends and issues in the development of alternatives to the use of animals in biomedical experimentation are discussed in this position paper. Eight topics are considered and include refinement of acute toxicity assays; eye corrosion/irritation alternatives; skin corrosion/irritation alternatives; contact sensitization alternatives; developmental/reproductive testing alternatives; genetic engineering (transgenic) assays; toxicogenomics; and validation of alternative methods. The discussion of refinement of acute toxicity assays is focused primarily on developments with regard to reduction of the number of animals used in the LD(50) assay. However, the substitution of humane endpoints such as clinical signs of toxicity for lethality in these assays is also evaluated. Alternative assays for eye corrosion/irritation as well as those for skin corrosion/irritation are described with particular attention paid to the outcomes, both successful and unsuccessful, of several validation efforts. Alternative assays for contact sensitization and developmental/reproductive toxicity are presented as examples of methods designed for the examination of interactions between toxins and somewhat more complex physiological systems. Moreover, genetic engineering and toxicogenomics are discussed with an eye toward the future of biological experimentation in general. The implications of gene manipulation for research animals, specifically, are also examined. Finally, validation methods are investigated as to their effectiveness, or lack thereof, and suggestions for their standardization and improvement, as well as implementation are reviewed.

  14. An Empirical Study Analyzing Job Productivity in Toxic Workplace Environments

    Directory of Open Access Journals (Sweden)

    Amna Anjum

    2018-05-01

    Full Text Available Purpose: This empirical study aims to determine the effects of a toxic workplace environment, which can negatively impact the job productivity of an employee. Methodology: Three hundred questionnaires were randomly distributed among the staff members of seven private universities in Pakistan with a final response rate of 89%. For analysis purposes, AMOS 22 was used to study the direct and indirect effects of the toxic workplace environment on job productivity. Confirmatory Factor Analysis (CFA was conducted to ensure the convergent and discriminant validity of the factors, while the Hayes mediation approach was used to verify the mediating role of job burnout between the four dimensions of toxic workplace environment and job productivity. A toxic workplace with multiple dimensions, such as workplace ostracism, workplace incivility, workplace harassment, and workplace bullying, was used in this study. Findings: By using the multiple statistical tools and techniques, it has been proven that ostracism, incivility, harassment, and bullying have direct negative significant effects on job productivity, while job burnout was shown to be a statistical significant mediator between the dimensions of a toxic workplace environment and job productivity. Finally, we concluded that organizations need to eradicate the factors of toxic workplace environments to ensure their prosperity and success. Practical Implications: This study encourages managers, leaders, and top management to adopt appropriate policies for enhancing employees’ productivity. Limitations: This study was conducted by using a cross-sectional research design. Future research aims to expand the study by using a longitudinal research design.

  15. Toxicity of some formation fluids and methods of rehabilitation subsequent to their spillage

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, D R

    1976-01-01

    This paper deals with the effects that formation fluids have on animal and plant life. Crude oil is a mixture--not only of hydrocarbons, but of suspended salts and of sulfur compounds. The toxicity of some of the hydrocarbons and some of the sulfur compounds is discussed, as is the toxicity of salt. Consideration is also given to the complexity of the hydrocarbon components and the influence of refining methods on toxicity. Some mechanisms by which an animal system may attempt to overcome injurious effects are outlined. Finally, methods of aiding recovery are suggested. 26 references.

  16. Animal and non-animal experiments in nanotechnology - the results of a critical literature survey.

    Science.gov (United States)

    Sauer, Ursula G

    2009-01-01

    A literature survey funded by the Foundation Animalfree Research was performed to obtain an overview on animal experiments in nanotechnology. Scientific articles from Germany, France, the United Kingdom, Italy, the Netherlands and Switzerland published between 2004 and 2007 were collected. A total of 164 articles was retrieved covering in vivo nanotechnological research. The majority of animal experiments were conducted in "nanomedicine", i.e. nanotechnology in the health care area, to study targeted drug, vaccine or gene delivery. Further areas of research relate to nanotechnology-based imaging technologies, the toxicity of nanomaterials, tissue engineering for regenerative treatments, and magnetic tumour thermotherapy. Many experiments were classified as moderately and even severely distressful to the animals. Due to the significance of the scientific topics pursued, the possible scientific benefit of the research depicted in the articles is also assigned to be moderate to high. Nevertheless, it has to be asked whether such animal experiments are truly the only means to answer the scientific questions addressed in nanotechnology. An overview on non-animal test methods used in nanotechnological research revealed a broad spectrum of methodologies applied in a broad spectrum of scientific areas, including those for which animal experiments are being performed. Explicit incentives to avoid animal experiments in nanotechnology currently can only be found in the area of nanotoxicology, but not in the area of nanomedicine. From the point of view of animal welfare, not least because of the new technologies that arise due to nanotechnology, it is time for a paradigm change both in fundamental and applied biomedical research to found research strategies on non-animal test methods.

  17. Cyanotoxins: producing organisms, occurrence, toxicity, mechanism of action and human health toxicological risk evaluation.

    Science.gov (United States)

    Buratti, Franca M; Manganelli, Maura; Vichi, Susanna; Stefanelli, Mara; Scardala, Simona; Testai, Emanuela; Funari, Enzo

    2017-03-01

    Cyanobacteria were present on the earth 3.5 billion years ago; since then they have colonized almost all terrestrial and aquatic ecosystems. They produce a high number of bioactive molecules, among which some are cyanotoxins. Cyanobacterial growth at high densities, forming blooms, is increasing in extension and frequency, following anthropogenic activities and climate changes, giving rise to some concern for human health and animal life exposed to cyanotoxins. Numerous cases of lethal poisonings have been associated with cyanotoxins ingestion in wild animal and livestock. In humans few episodes of lethal or severe human poisonings have been recorded after acute or short-term exposure, but the repeated/chronic exposure to low cyanotoxin levels remains a critical issue. The properties of the most frequently detected cyanotoxins (namely, microcystins, nodularins, cylindrospermopsin and neurotoxins) are here critically reviewed, describing for each toxin the available information on producing organisms, biosynthesis/genetic and occurrence, with a focus on the toxicological profile (including kinetics, acute systemic toxicity, mechanism and mode of action, local effects, repeated toxicity, genotoxicity, carcinogenicity, reproductive toxicity; human health effects and epidemiological studies; animal poisoning) with the derivation of health-based values and considerations on the risks for human health.

  18. Reduction of Fumonisin Toxicity by Extrusion and Nixtamalization (Alkaline Cooking)

    Science.gov (United States)

    Fumonisins are found in corn. They are toxic to animals, cause cancer in rodents, and neural tube defects in LM/Bc mice. Reducing their concentrations in corn-based foods is therefore desirable. Chemical analysis or in vitro bioassays of food extracts might not detect toxic fumonisin reaction pro...

  19. Temperature influence on chemical toxicity to aquatic organisms

    International Nuclear Information System (INIS)

    Cairns, J. Jr.; Heath, A.G.; Parker, B.C.

    1975-01-01

    The literature on the effects of temperature on chemical toxicity to aquatic animals and microorganisms is reviewed. Microbial photosynthesis and respiration is briefly discussed. It is concluded that there is a paucity of information on the inter-relations of temperature and toxicants to algae, bacteria, and protozoa and that standards based on the in situ response of indigenous organisms to specific discharge areas should be developed

  20. Atmospheric deposition exposes Qinling pandas to toxic pollutants.

    Science.gov (United States)

    Chen, Yi-Ping; Zheng, Ying-Juan; Liu, Qiang; Song, Yi; An, Zhi-Sheng; Ma, Qing-Yi; Ellison, Aaron M

    2017-03-01

    The giant panda (Ailuropoda melanoleuca) is one of the most endangered animals in the world, and it is recognized worldwide as a symbol for conservation. A previous study showed that wild and captive pandas, especially those of the Qinling subspecies, were exposed to toxicants in their diet of bamboo; the ultimate origin of these toxicants is unknown. Here we show that atmospheric deposition is the most likely origin of heavy metals and persistent organic pollutants (POPs) in the diets of captive and wild Qinling pandas. Average atmospheric deposition was 199, 115, and 49 g·m -2 ·yr -1 in the center of Xi'an City, at China's Shaanxi Wild Animal Research Center (SWARC), and at Foping National Nature Reserve (FNNR), respectively. Atmospheric deposition of heavy metals (As, Cd, Cr, Pb, Hg, Co, Cu, Zn, Mn, and Ni) and POPs was highest at Xi'an City, intermediate at SWARC, and lowest at FNNR. Soil concentrations of the aforementioned heavy metals other than As and Zn also were significantly higher at SWARC than at FNNR. Efforts to conserve Qinling pandas may be compromised by air pollution attendant to China's economic development. Improvement of air quality and reductions of toxic emissions are urgently required to protect China's iconic species. © 2017 by the Ecological Society of America.

  1. ROS dependent copper toxicity in Hydra-biochemical and molecular study.

    Science.gov (United States)

    Zeeshan, Mohammed; Murugadas, Anbazhagan; Ghaskadbi, Surendra; Rajendran, Ramasamy Babu; Akbarsha, Mohammad Abdulkader

    2016-01-01

    Copper, an essential microelement, is known to be toxic to aquatic life at concentrations higher than that could be tolerated. Copper-induced oxidative stress has been documented in vitro, yet the in vivo effects of metal-induced oxidative stress have not been extensively studied in the lower invertebrates. The objective of the present study has been to find the effect of ROS-mediated toxicity of environmentally relevant concentrations of copper at organismal and cellular levels in Hydra magnipapillata. Exposure to copper at sublethal concentrations (0.06 and 0.1mg/L) for 24 or 48h resulted in generation of significant levels of intracellular reactive oxygen species (ROS). We infer that the free radicals here originate predominantly at the lysosomes but partly at the mitochondria also as visualized by H2-DHCFDA staining. Quantitative real-time PCR of RNA extracted from copper-exposed polyps revealed dose-dependent up-regulation of all antioxidant response genes (CAT, SOD, GPx, GST, GR, G6PD). Concurrent increase of Hsp70 and FoxO genes suggests the ability of polyps to respond to stress, which at 48h was not the same as at 24h. Interestingly, the transcript levels of all genes were down-regulated at 48h as compared to 24h incubation period. Comet assay indicated copper as a powerful genotoxicant, and the DNA damage was dose- as well as duration-dependent. Western blotting of proteins (Bax, Bcl-2 and caspase-3) confirmed ROS-mediated mitochondrial cell death in copper-exposed animals. These changes correlated well with changes in morphology, regeneration and aspects of reproduction. Taken together, the results indicate increased production of intracellular ROS in Hydra on copper exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Safety assessment of hydroethanolic rambutan rind extract: acute and sub-chronic toxicity studies.

    Science.gov (United States)

    Thinkratok, Aree; Suwannaprapha, Parin; Srisawat, Rungrudee

    2014-10-01

    This study evaluated the safety of rambutan rind extract (RRE) in male Wistar rats. While acute toxicity was evaluated by feeding the rats with single doses of RRE (1000, 2000, 3000, 4000, and 5000 mg/kg) and its sub-chronic toxicity was observed in rats orally administered with RRE (500, 1000, and 2000 mg/kg) daily for 30 days. In acute toxicity study, the LD50 was found to be greater than 5000 mg/kg of RRE. In sub-chronic toxicity study, no mortality and sign of toxicity was found up to 1000 mg/kg/day of RRE. At 2000 mg/kg/day dose, the mortality rate was 12.5%. Significant decreases in body weight gain and food consumption were found in both acute and sub-chronic toxicity studies. In acute toxicity study, all the studied doses of RRE did not alter serum levels of triglyceride (TG), aspartate aminotransferase (AST) andalanine aminotransferase (ALT). In sub-chronic toxicity study, all studied doses of RRE significantly decreased plasma levels of TG and blood urea nitrogen, but did not alter plasma levels of AST and ALT. TC levels did not show any significant change in both the studies. The obtained results provide basic information for in vivo experimental studies of the pharmacological potentiality of RRE.

  3. TOXICITY BEHAVIORS IN ORGANIZATIONS: STUDY OF RELIABILITY AND VALIDITY OF TOXIC EMOTIONAL EXPERIENCES SCALE

    OpenAIRE

    Bektas, Meral; Erkal, Pinar

    2016-01-01

    In toxic organizations which are mostly destructive instead of being constrictive towards its employees, toxicity behaviors emerge as a result of the formal and informal relationships. Toxicity behaviors are often negatively affect motivation, job satisfaction or performance of the employees in workplace. Basic toxicity behaviors in organizations are: extreme jealousy, biting words, emphasis  superiority emphasis, getting angry, offending employees, strict control, heavy job workload, limited...

  4. CYP 2E1 mutant mice are resistant to DDC-induced enhancement of MPTP toxicity.

    Science.gov (United States)

    Viaggi, C; Vaglini, F; Pardini, C; Sgadò, P; Caramelli, A; Corsini, G U

    2007-01-01

    In order to reach a deeper insight into the mechanism of diethyldithiocarbamate (DDC)-induced enhancement of MPTP toxicity in mice, we showed that CYP450 (2E1) inhibitors, such as diallyl sulfide (DAS) or phenylethylisothiocyanate (PIC), also potentiate the selective DA neuron degeneration in C57/bl mice. Furthermore we showed that CYP 2E1 is present in the brain and in the basal ganglia of mice (Vaglini et al., 2004). However, because DAS and PIC are not selective CYP 2E1 inhibitors and in order to provide direct evidence for CYP 2E1 involvement in the enhancement of MPTP toxicity, CYP 2E1 knockout mice (GONZ) and wild type animals (SVI) of the same genetic background were treated with MPTP or the combined DDC + MPTP treatment. In CYP 2E1 knockout mice, DDC pretreatment completely fails to enhance MPTP toxicity, although enhancement of MPTP toxicity was regularly present in the SVI control animals. The immunohistochemical study confirms our results and suggests that CYP 2E1 may have a detoxifying role.

  5. [Non-animal toxicology in the safety testing of chemicals].

    Science.gov (United States)

    Heinonen, Tuula; Tähti, Hanna

    2013-01-01

    There is an urgent need to develop predictive test methods better than animal experiments for assessing the safety of chemical substances to man. According to today's vision this is achieved by using human cell based tissue and organ models. In the new testing strategy the toxic effects are assessed by the changes in the critical parameters of the cellular biochemical routes (AOP, adverse toxic outcome pathway-principle) in the target tissues. In vitro-tests are rapid and effective, and with them automation can be applied. The change in the testing paradigm is supported by all stakeholders: scientists, regulators and people concerned on animal welfare.

  6. Acute And Subchronic Toxicity Studies Of SNEDDS (Self Nanoemulsifying Drug Delivery Systems) From Ethyl Acetate Extract Of Bay Leaf (Eugenia polyantha W.) with Virgin Coconut Oil As Oil Phase

    Science.gov (United States)

    Prihapsara, F.; Alamsyah, R. I.; Widiyani, T.; Artanti, A. N.

    2018-03-01

    Bay leaf (Eugenia polyantha) is widely used as an alternative therapy for diabetic and hypercholesterol. However, the administration of the extract has a low oral bioavailability, therefore it is prepared by Self Nanoemulsifying Drug Delivery Systems (SNEDDS) ethyl acetate extract of bay leaf. Therefore, acute and subchronic toxicity test is required. The toxicity test performed was an experimental study, including acute and subchronic toxicity tests. Animal experiments were used using Wistar strain rats. Acute toxicity test using 5 groups (n=5) consisted of 1 control group and 4 groups of SNEDDS dose with 48 mg/kgBW 240 mg/kg, 1200 mg/kg, and 6000 mg/kg, while for subchronic toxicity test with 1 group control and 3 groups of doses of SNEDDS with dose group variation 91.75 mg/kgBW, 183.5 mg/kg, and 367 mg/kg. Duration of observation at acute toxicity test for 14 days while for subcronic toxicity test for 28 days with continuous SNEDDS dosage. The results of the acute toxicity test showed toxic symptoms and obtained median lethal dose (LD50) values from SNEDDS from ethyl acetate extract of bay leaf 1409.30 mg/kgBW belonging to slightly toxic category. Subchronic toxicity studies show that the test drug has minor damage in liver and kidneys and moderate damage in pancreas.

  7. Oral Chromium Exposure and Toxicity

    Science.gov (United States)

    Sun, Hong; Brocato, Jason

    2015-01-01

    Hexavalent chromium [Cr(VI)] is a known carcinogen when inhaled. However, inhalational exposure to Cr(VI) affects only a small portion of the population, mainly by occupational exposures. In contrast, oral exposure to Cr(VI) is widespread and affects many people throughout the globe. In 2008, the National Toxicology Program (NTP) released a 2-year study demonstrating that ingested Cr(VI) was carcinogenic in rats and mice. The effects of Cr(VI) oral exposure is mitigated by reduction in the gut, however a portion evades the reductive detoxification and reaches target tissues. Once Cr(VI) enters the cell, it ultimately gets reduced to Cr(III), which mediates its toxicity via induction of oxidative stress during the reduction while Cr intermediates react with protein and DNA. Cr(III) can form adducts with DNA that may lead to mutations. This review will discuss the potential adverse effects of oral exposure to Cr(VI) by presenting up-to-date human and animal studies, examining the underlying mechanisms that mediate Cr(VI) toxicity, as well as highlighting opportunities for future research. PMID:26231506

  8. Modification of metal bioaccumulation and toxicity in Daphnia magna by titanium dioxide nanoparticles

    International Nuclear Information System (INIS)

    Tan, Cheng; Wang, Wen-Xiong

    2014-01-01

    Titanium dioxide (TiO 2 ) nanoparticles are widely used in water treatments, yet their influences on other contaminants in the water are not well studied. In this study, the aqueous uptake, assimilation efficiency, and toxicity of two ionic metals (cadmium-Cd, and zinc-Zn) in a freshwater zooplankton, Daphnia magna, were investigated following 2 days pre-exposure to nano-TiO 2 . Pre-exposure to 1 mg/L nano-TiO 2 resulted in a significant increase in Cd and Zn uptake from the dissolved phase. After the nano-TiO 2 in the guts were cleared, the uptake rates immediately recovered to the normal levels. Concurrent measurements of reactive oxygen species (ROS) and metallothioneins (MTs) suggested that the increased metal uptake was mainly due to the increased number of binding sites provided by nano-TiO 2 presented in the guts. Consistently, pre-exposure to nano-TiO 2 increased the toxicity of aqueous Cd and Zn due to enhanced uptake. Our study provides the evidence that nano-TiO 2 in the guts of animals could increase the uptake and toxicity of other contaminants. -- Highlights: • Dissolved Cd and Zn uptake in daphnids increased significantly after nano-TiO 2 pre-exposure. • Aqueous toxicity of Cd and Zn also increased after nano-TiO 2 pre-exposure. • Dietary assimilation of Cd and Zn was not affected after nano-TiO 2 pre-exposure. • Metal uptake recovered to normal levels after nano-TiO 2 in the guts were removed. • Nano-TiO 2 in the guts of animals could increase the uptake and toxicity of other contaminants. -- Nano-TiO 2 accumulation in Daphnia magna facilitated the uptake and toxicity of metal contaminants

  9. Evaluation of the acute toxicity of refined petroleum products against ...

    African Journals Online (AJOL)

    Static and static-renewal evaluation of the acute toxicity of three refined petroleum products — petrol, kerosene and diesel — against two freshwater animals, the mollusc Pila ovata and the fish Poecilia reticulata, was conducted in the laboratory. Petrol, kerosene and diesel were found to be moderately toxic to the test ...

  10. Effect of surfactant in mitigating cadmium oxide nanoparticle toxicity: Implications for mitigating cadmium toxicity in environment

    International Nuclear Information System (INIS)

    Balmuri, Sricharani Rao; Selvaraj, Uthra; Kumar, Vadivel Vinod; Anthony, Savarimuthu Philip; Tsatsakis, Aristides Michael; Golokhvast, Kirill Sergeevich; Raman, Thiagarajan

    2017-01-01

    Cadmium (Cd), classified as human carcinogen, is an extremely toxic heavy metal pollutant, and there is an increasing environmental concern for cadmium exposure through anthropogenic sources including cigarette smoke. Though Cd based nanoparticles such as cadmium oxide (CdO) are being widely used in a variety of clinical and industrial applications, the toxicity of CdO nanoparticles has not been well characterized. Herein we report the toxicity of CdO nanoparticles employing zebrafish as a model. Two different CdO nanoparticles were prepared, calcination of Cd(OH) 2 without any organic molecule (CdO-1) and calcination of Cd-citrate coordination polymer (CdO-2), to evaluate and compare the toxicity of these two different CdO nanoparticles. Results show that zebrafish exposed to CdO-2 nanoparticles expressed reduced toxicity as judged by lower oxidative stress levels, rescue of liver carboxylesterases and reduction in metallothionein activity compared to CdO-1 nanoparticles. Histopathological observations also support our contention that CdO-1 nanoparticles showed higher toxicity relative to CdO-2 nanoparticles. The organic unit of Cd-citrate coordination polymer might have converted into carbon during calcination that might have covered the surface of CdO nanoparticles. This carbon surface coverage can control the release of Cd 2+ ions in CdO-2 compared to non-covered CdO-1 nanoparticles and hence mitigate the toxicity in the case of CdO-2. This was supported by atomic absorption spectrophotometer analyses of Cd 2+ ions release from CdO-1 and CdO-2 nanoparticles. Thus the present study clearly demonstrates the toxicity of CdO nanoparticles in an aquatic animal and also indicates that the toxicity could be substantially reduced by carbon coverage. This could have important implications in terms of anthropogenic release and environmental pollution caused by Cd and human exposure to Cd 2+ from sources such as cigarette smoke. - Highlights: • Toxicity of Cd

  11. Effect of surfactant in mitigating cadmium oxide nanoparticle toxicity: Implications for mitigating cadmium toxicity in environment

    Energy Technology Data Exchange (ETDEWEB)

    Balmuri, Sricharani Rao [Department of Bioengineering, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India); Selvaraj, Uthra [Department of Biotechnology, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India); Kumar, Vadivel Vinod [Department of Chemistry, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India); Anthony, Savarimuthu Philip, E-mail: philip@biotech.sastra.edu [Department of Chemistry, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India); Tsatsakis, Aristides Michael [Department of Forensic Sciences and Toxicology, Medical School, University of Crete, Heraklion 71003 (Greece); Scientific Educational Center of Nanotechnology, Far Eastern Federal University, Vladivostok 690990 (Russian Federation); Golokhvast, Kirill Sergeevich [Scientific Educational Center of Nanotechnology, Far Eastern Federal University, Vladivostok 690990 (Russian Federation); Raman, Thiagarajan, E-mail: raman@biotech.sastra.edu [Department of Bioengineering, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India); Centre for Research in Infectious Diseases (CRID), School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401 (India)

    2017-01-15

    Cadmium (Cd), classified as human carcinogen, is an extremely toxic heavy metal pollutant, and there is an increasing environmental concern for cadmium exposure through anthropogenic sources including cigarette smoke. Though Cd based nanoparticles such as cadmium oxide (CdO) are being widely used in a variety of clinical and industrial applications, the toxicity of CdO nanoparticles has not been well characterized. Herein we report the toxicity of CdO nanoparticles employing zebrafish as a model. Two different CdO nanoparticles were prepared, calcination of Cd(OH){sub 2} without any organic molecule (CdO-1) and calcination of Cd-citrate coordination polymer (CdO-2), to evaluate and compare the toxicity of these two different CdO nanoparticles. Results show that zebrafish exposed to CdO-2 nanoparticles expressed reduced toxicity as judged by lower oxidative stress levels, rescue of liver carboxylesterases and reduction in metallothionein activity compared to CdO-1 nanoparticles. Histopathological observations also support our contention that CdO-1 nanoparticles showed higher toxicity relative to CdO-2 nanoparticles. The organic unit of Cd-citrate coordination polymer might have converted into carbon during calcination that might have covered the surface of CdO nanoparticles. This carbon surface coverage can control the release of Cd{sup 2+} ions in CdO-2 compared to non-covered CdO-1 nanoparticles and hence mitigate the toxicity in the case of CdO-2. This was supported by atomic absorption spectrophotometer analyses of Cd{sup 2+} ions release from CdO-1 and CdO-2 nanoparticles. Thus the present study clearly demonstrates the toxicity of CdO nanoparticles in an aquatic animal and also indicates that the toxicity could be substantially reduced by carbon coverage. This could have important implications in terms of anthropogenic release and environmental pollution caused by Cd and human exposure to Cd{sup 2+} from sources such as cigarette smoke. - Highlights:

  12. Aflatoxin Toxicity Reduction in Feed by Enhanced Binding to Surface-Modified Clay Additives

    Science.gov (United States)

    Jaynes, William F.; Zartman, Richard E.

    2011-01-01

    Animal feeding studies have demonstrated that clay additives, such as bentonites, can bind aflatoxins in ingested feed and reduce or eliminate the toxicity. Bentonite deposits are found throughout the world and mostly consist of expandable smectite minerals, such as montmorillonite. The surfaces of smectite minerals can be treated with organic compounds to create surface-modified clays that more readily bind some contaminants than the untreated clay. Montmorillonites treated with organic cations, such as hexadecyltrimethylammonium (HDTMA) and phenyltrimethylammonium (PTMA), more effectively remove organic contaminants, such as benzene and toluene, from water than untreated clay. Similarly, montmorillonite treated with PTMA (Kd = 24,100) retained more aflatoxin B1 (AfB1) from aqueous corn flour than untreated montmorillonite (Kd = 944). Feed additives that reduced aflatoxin toxicity in animal feeding studies adsorbed more AfB1 from aqueous corn flour than feed additives that were less effective. The organic cations HDTMA and PTMA are considered toxic and would not be suitable for clay additives used in feed or food, but other non-toxic or nutrient compounds can be used to prepare surface-modified clays. Montmorillonite (SWy) treated with choline (Kd = 13,800) and carnitine (Kd = 3960) adsorbed much more AfB1 from aqueous corn flour than the untreated clay (Kd = 944). A choline-treated clay prepared from a reduced-charge, high-charge montmorillonite (Kd = 20,100) adsorbed more AfB1 than the choline-treated high-charge montmorillonite (Kd = 1340) or the untreated montmorillonite (Kd = 293). Surface-modified clay additives prepared using low-charge smectites and nutrient or non-toxic organic compounds might be used to more effectively bind aflatoxins in contaminated feed or food and prevent toxicity. PMID:22069725

  13. Acute oral Toxicity and Antioxidant Activity of Neoglaziovia variegata

    African Journals Online (AJOL)

    fisiologia

    2012-09-18

    Sep 18, 2012 ... In the acute toxicity of Nv-EtOH, behavioral and physiological alterations were not observed neither animal's death in the doses of 2.0 g/kg intraperitoneally and 5.0 g/kg orally, respectively indicating low toxicity of the extract. In this experiment, it was observed that the. Nv-EtOH has LD50 > 5000 mg/kg.

  14. Redução, refinamento e substituição do uso de animais em estudos toxicológicos: uma abordagem atual Reduction, refinement and replacement of animal use in toxicity testing: an overview

    Directory of Open Access Journals (Sweden)

    Karen Cristine Ceroni Cazarin

    2004-09-01

    Full Text Available A avaliação da toxicidade de uma substância é realizada com o objetivo de predizer os efeitos nocivos que a mesma poderá desencadear quando da exposição humana pelas diversas vias. Para cumprir este propósito, o modelo animal é o mais utilizado nos estudos toxicológicos e requerido nos processos investigativos. Entretanto, a utilização de animais na pesquisa tem sido razão de diversas discussões em função do grande número necessário e do sofrimento causado, principalmente em relação aos estudos de toxicidade aguda. Existe uma tendência mundial para reavaliar a utilização de animais nos experimentos, concretizada a partir de um programa denominado de 3Rs (Reduction, Refinement, Replacement, que objetiva além de diminuir o número de animais, minimizar a dor e o desconforto e buscar alternativas para a substituição dos testes in vivo. Diversas metodologias alternativas já foram implantadas, sendo este um processo complexo que abrange desde o seu desenvolvimento até sua aceitação regulatória e adoção por diversas organizações. Sendo assim, o presente trabalho apresenta abordagem atualizada do Programa 3Rs, com ênfase na sua evolução histórica e nos processos de implantação e validação de métodos alternativos, principalmente aplicados no contexto da avaliação da toxicidade, enfatizando sua importância e utilidade frente à tendência global de harmonização.Toxicity assessment is the process of predicting the adverse effects that may be caused to an organism by exposuring it to a given chemical and, for regulation purposes, the most used model in toxicity testing is the animal. However, in today's society the use of animals has become a subject of much public health due to the large number of animals used as well as the pain and distress caused, mainly related to acute toxicity testing. The concept of the "Three Rs" - reduction, refinement, and replacement of animal use - emerged as a mean of removing

  15. Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing.

    Science.gov (United States)

    Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

    2017-06-01

    Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Recent advances in graphene family materials toxicity investigations

    International Nuclear Information System (INIS)

    Jastrzębska, Agnieszka Maria; Kurtycz, Patrycja; Olszyna, Andrzej Roman

    2012-01-01

    Recently, graphene family materials (GFMs) have been introduced among all fields of science and still get numerous attention. Also, the applicability of these materials in many areas makes them very attractive. GFMs have attracted both academic and industrial interest as they can produce a dramatic improvement in materials properties at very low filler content. This article presents recent findings on GFMs toxicity properties based on the most current literature. This article studies the effects of GFMs on bacteria, mammalian cells, animals, and plants. This article also reviews in vitro and in vivo test results as well as potential anticancer activity and toxicity mechanisms of GFMs. The effect of functionalization of graphene on pacifying its strong interactions with cells and associated toxic effects was also analyzed. The authors of the article believe that further work should focus on in vitro and in vivo studies on possible interactions between GFMs and different living systems. Further research should also focus on decreasing GFMs toxicity, which still poses a great challenge for in vivo biomedical applications. Consequently, the potential impact of graphene and its derivatives on humans and environmental health is a matter of academic interest. However, potential hazards sufficient for risk assessment first need to be investigated.

  17. Harmful Effects of Nanoparticles on Animals

    Directory of Open Access Journals (Sweden)

    Jean-Marie Exbrayat

    2015-01-01

    Full Text Available Since several years nanoparticles (NPs are produced by industries and used in several fields of activities. They are finally found in aquatic and terrestrial environments, where they are ingested by living organisms in which they accumulate, before being eliminated. In organisms, NPs represent foreign elements with their own physicochemical properties due to their small size. So NPs may interfere with the normal physiological mechanisms of the embryos, growing animals, and adults, and it is indispensable to understand their potentially direct or indirect harmful effects on living organisms. It has been already shown that NPs could be toxic to bacteria, algae, invertebrates, and vertebrates. In this review, several examples of recent studies are given. We will examine successively the effects of NPs on terrestrial and semiaquatic and aquatic vertebrate and invertebrate animals.

  18. The Toxicity of Depleted Uranium

    Directory of Open Access Journals (Sweden)

    Wayne Briner

    2010-01-01

    Full Text Available Depleted uranium (DU is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a clear and defined set of symptoms. Chronic low-dose, or subacute, exposure to depleted uranium alters the appearance of milestones in developing organisms. Adult animals that were exposed to depleted uranium during development display persistent alterations in behavior, even after cessation of depleted uranium exposure. Adult animals exposed to depleted uranium demonstrate altered behaviors and a variety of alterations to brain chemistry. Despite its reduced level of radioactivity evidence continues to accumulate that depleted uranium, if ingested, may pose a radiologic hazard. The current state of knowledge concerning DU is discussed.

  19. Animal subjectivity : a study into philosophy and theory of animal experience

    NARCIS (Netherlands)

    Lijmbach, S.

    1998-01-01

    For many people, laypeople as well as animal scientists and philosophers, animal welfare involves animal feelings. Scientifically, however, animal feelings are problematic. In the concluding remarks of a conference about the welfare of domestic animals in 1994, for example, two questions

  20. The Role of Oxidative Stress in Methamphetamine-induced Toxicity and Sources of Variation in the Design of Animal Studies.

    Science.gov (United States)

    McDonnell-Dowling, Kate; Kelly, John P

    2017-01-01

    The prevalence of methamphetamine (MA) use has increased in recent years. In order to assess how this drug produces its effects, both clinical and preclinical studies have recently begun to focus on oxidative stress as an important biochemical mechanism in mediating these effects. The purpose of this review is to illustrate the variation in the design of preclinical studies investigating MA exposure on oxidative stress parameters in animal models. The experimental variables investigated and summarised include MA drug treatment, measurements of oxidative stress and antioxidant treatments that ameliorate the harmful effects of MA. These preclinical studies differ greatly in their experimental design with respect to the dose of MA (ranging between 0.25 and 20 mg/kg), the dosing regime (acute, binge or chronic), the time of measurement of oxidative stress (0.5 h to 2 wks after last MA administration), the antioxidant system targeted and finally the use of antioxidants including the route of administration (i.p. or p.o.), the frequency of exposure and the time of exposure (preventative or therapeutic). The findings in this paper suggest that there is a large diversity among these studies and so the interpretation of these results is challenging. For this reason, the development of guidelines and how best to assess oxidative stress in animal models may be beneficial. The use of these simple recommendations mean that results will be more comparable between laboratories and that future results generated will give us a greater understanding of the contribution of this important biochemical mechanism and its implications for the clinical scenario.

  1. Subchronic toxicity study in vivo and allergenicity study in vitro for genetically modified rice that expresses pharmaceutical protein (human serum albumin).

    Science.gov (United States)

    Sheng, Yao; Qi, Xiaozhe; Liu, Yifei; Guo, Mingzhang; Chen, Siyuan; He, Xiaoyun; Huang, Kunlun; Xu, Wentao

    2014-10-01

    Genetically modified (GM) crops that express pharmaceutical proteins have become an important focus of recent genetic engineering research. Food safety assessment is necessary for the commercial development of these crops. Subchronic toxicity study in vivo and allergenicity study in vitro were designed to evaluate the food safety of the rice variety expressing human serum albumin (HSA). Animals were fed rodent diets containing 12.5%, 25.0% and 50.0% GM or non-GM rice for 90 days. The composition analysis of the GM rice demonstrated several significant differences. However, most of the differences remained within the ranges reported in the literature. In the animal study, a range of indexes including clinical observation, feed efficiency, hematology, serum chemistry, organ weights and histopathology were examined. Random changes unrelated to the GM rice exposure, within the range of historical control values and not associated with any signs of illness were observed. The results of heat stability and in vitro digestion of HSA indicated no evidence of potential allergenicity of the protein. Overall, the results of these studies suggest that the GM rice appears to be safe as a dietary ingredient when it is used at up to 50% in the diet on a subchronic basis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Predicting human developmental toxicity of pharmaceuticals using human embryonic stem cells and metabolomics

    International Nuclear Information System (INIS)

    West, Paul R.; Weir, April M.; Smith, Alan M.; Donley, Elizabeth L.R.; Cezar, Gabriela G.

    2010-01-01

    Teratogens, substances that may cause fetal abnormalities during development, are responsible for a significant number of birth defects. Animal models used to predict teratogenicity often do not faithfully correlate to human response. Here, we seek to develop a more predictive developmental toxicity model based on an in vitro method that utilizes both human embryonic stem (hES) cells and metabolomics to discover biomarkers of developmental toxicity. We developed a method where hES cells were dosed with several drugs of known teratogenicity then LC-MS analysis was performed to measure changes in abundance levels of small molecules in response to drug dosing. Statistical analysis was employed to select for specific mass features that can provide a prediction of the developmental toxicity of a substance. These molecules can serve as biomarkers of developmental toxicity, leading to better prediction of teratogenicity. In particular, our work shows a correlation between teratogenicity and changes of greater than 10% in the ratio of arginine to asymmetric dimethylarginine levels. In addition, this study resulted in the establishment of a predictive model based on the most informative mass features. This model was subsequently tested for its predictive accuracy in two blinded studies using eight drugs of known teratogenicity, where it correctly predicted the teratogenicity for seven of the eight drugs. Thus, our initial data shows that this platform is a robust alternative to animal and other in vitro models for the prediction of the developmental toxicity of chemicals that may also provide invaluable information about the underlying biochemical pathways.

  3. Toxicity studies of Cordia salicifolia extract Estudo da toxidade do extrato de Cordia salicifolia

    Directory of Open Access Journals (Sweden)

    Roberto Kenji Nakamura Cuman

    2005-03-01

    Full Text Available Este estudo foi realizado para determinar a toxicidade aguda do extrato total de Cordia salicifolia (DL50 após administração oral e intraperitoneal em camundongos, assim como os efeitos do extrato sobre alguns parâmetros bioquímicos no plasma de ratos após um tratamento prolongado (90 dias. A DL50 do extrato administrado por v.o. foi maior que 2000 mg/Kg, enquanto a DL50 por via i.p. foi aproximadamente 920 mg/Kg. A administração oral diária do extrato nas doses de 20, 100, 200 e 400 mg/kg por um período de 90 dias não causou modificações no ganho de peso corporal, no peso dos órgãos, nos parâmetros hematológicos e bioquímicos dos animais. Estes resultados indicam que a administração do extrato por um período mais prolongado não provocou efeitos de toxicidade nos animaisThis study was carried out to determine the acute toxicity of the whole Cordia salicifolia extract (LD50 after oral and intraperitoneal administration in mice, and its effect on certain biochemical parameters in the plasma of rats after 90 days of administration. The oral LD50 value of the extract was higher than 2000 mg/kg while the LD50 by intraperitoneal injections was about 920 mg/kg. A daily oral administration of extracts at 20, 100, 200 and 400 mg/kg doses for 90 days did not cause significant changes in the body weight gain, organs weight or biochemical assays and hematology in the animals. The results showed that the administration of the extract for a prolonged period did not produce toxic effects in the animals

  4. Copper carrier protein in copper toxic sheep liver

    Energy Technology Data Exchange (ETDEWEB)

    Harris, A L; Dean, P D.G.

    1973-01-01

    The livers of copper-toxic sheep have been analyzed by gel electrophoresis followed by staining the gels for copper with diethyldithiocarbamate and for protein with amido schwartz. These gels were compared with similar gels obtained from the livers of normal and copper-deficient animals. The copper-toxic livers contained an extra protein band which possessed relatively weakly bound copper. Possible origins of this protein are discussed. 8 references, 1 figure, 2 tables.

  5. Do diosgenin ameliorate urinary bladder toxic effect of ...

    African Journals Online (AJOL)

    SWEET

    2012-01-26

    Jan 26, 2012 ... experimental animal models? ... BSO doses using a Swiss albino mouse model. Toxicity modulation ... bladder inflammation induced by CP in rats and mice .... 0.1 ml NADPH (nicotinamide adenine dinucleotide phosphate.

  6. Preliminary phytochemical, acute oral toxicity and antihepatotoxic study of roots of Paeonia officinalis Linn.

    Science.gov (United States)

    Ahmad, Feroz; Tabassum, Nahida

    2013-01-01

    To carry out a preliminary phytochemical, acute oral toxicity and antihepatotoxic study of the roots of Paeonia officinalis (P. officinalis) L. Preliminary phytochemical investigation was done as per standard procedures. Acute oral toxicity study was conducted as per OECD 425 guidelines. The antihepatotoxic activity of aqueous extract of root of P. officinalis was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in rats. Aqueous extract of P. officinalis at the dose levels of 100 and 200 mg/kg body weight was administered daily for 14 d in experimental animals. Liver injury was induced chemically, by CCl4 administration (1 mL/kg i.p.). The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum alkaline phosphatase (SALP), total bilirubin and total protein (TP) along with histopathological studies. Phytochemical screening revealed that the roots of P. officinalis contain alkaloids, tannins, saponins, glycosides, carbohydrates, flavonoids, terpenes, steroids and proteins. The aqueous extract did not cause any mortality up to 2 000 mg/kg. In rats that had received the root extract at the dose of 100 and 200 mg/kg, the substantially elevated AST, ALT, SALP, total bilirubin levels were significantly lowered, respectively, in a dose dependent manner, along with CCl4 while TP levels were elevated in these groups. Histopathology revealed regeneration of the livers in extract treated groups while Silymarin treated rats were almost normal. The aqueous extract of P. officinalis is safe and possesses antihepatotoxic potential.

  7. Refinery water (intake and effluent) quality: Update of 1970s with 1990s toxicity testing

    International Nuclear Information System (INIS)

    Chapman, P.M.; Paine, M.D.; Moran, T.; Kierstead, T.

    1994-01-01

    The quality of two separate refinery intake waters and effluents was investigated: Petro-Canada (Oakville) and Novacor (Corunna Operations). This study comprised eight different test organized and 22 different toxicity end points, was built on and complemented pioneering 1970s work at the Petro-Canada refinery, and was designed to (a) determine any changes in effluent quality, (b) determine any previously unsuspected effluent toxicity, and (c) determine any potential for chronic toxicity in the effluent. Although Petro-Canada has steadily reduced contaminants in its effluent since the earlier study, toxicity has not changed and no new toxic effects were identified. Effect thresholds for the most sensitive animal species (Daphnia pulex) were 1 to 10% effluent in both studies. The Novacor effluent had lesser effects on biota than the Petro-Canada effluent. Intake waters demonstrated toxicity in some tests. Chronic effects on invertebrates and fish in receiving waters are predicted not to occur in the Novacor effluent is diluted 10- to 20-fold and the Petro-Canada effluent is diluted 50- to 100-fold

  8. The classification of motor neuron defects in the zebrafish embryo toxicity test (ZFET) as an animal alternative approach to assess developmental neurotoxicity.

    Science.gov (United States)

    Muth-Köhne, Elke; Wichmann, Arne; Delov, Vera; Fenske, Martina

    2012-07-01

    Rodents are widely used to test the developmental neurotoxicity potential of chemical substances. The regulatory test procedures are elaborate and the requirement of numerous animals is ethically disputable. Therefore, non-animal alternatives are highly desirable, but appropriate test systems that meet regulatory demands are not yet available. Hence, we have developed a new developmental neurotoxicity assay based on specific whole-mount immunostainings of primary and secondary motor neurons (using the monoclonal antibodies znp1 and zn8) in zebrafish embryos. By classifying the motor neuron defects, we evaluated the severity of the neurotoxic damage to individual primary and secondary motor neurons caused by chemical exposure and determined the corresponding effect concentration values (EC₅₀). In a proof-of-principle study, we investigated the effects of three model compounds thiocyclam, cartap and disulfiram, which show some neurotoxicity-indicating effects in vertebrates, and the positive controls ethanol and nicotine and the negative controls 3,4-dichloroaniline (3,4-DCA) and triclosan. As a quantitative measure of the neurotoxic potential of the test compounds, we calculated the ratios of the EC₅₀ values for motor neuron defects and the cumulative malformations, as determined in a zebrafish embryo toxicity test (zFET). Based on this index, disulfiram was classified as the most potent and thiocyclam as the least potent developmental neurotoxin. The index also confirmed the control compounds as positive and negative neurotoxicants. Our findings demonstrate that this index can be used to reliably distinguish between neurotoxic and non-neurotoxic chemicals and provide a sound estimate for the neurodevelopmental hazard potential of a chemical. The demonstrated method can be a feasible approach to reduce the number of animals used in developmental neurotoxicity evaluation procedures. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Ending the use of animals in toxicity testing and risk evaluation.

    Science.gov (United States)

    Rowan, Andrew N

    2015-10-01

    This article discusses the use of animals for the safety testing of chemicals, including pharmaceuticals, household products, pesticides, and industrial chemicals. It reviews changes in safety testing technology and what those changes mean from the perspective of industrial innovation, public policy and public health, economics, and ethics. It concludes that the continuing use of animals for chemical safety testing should end within the decade as cheaper, quicker, and more predictive technologies are developed and applied.

  10. A two-generation inhalation reproductive toxicity study upon the exposure to manganese chloride.

    Science.gov (United States)

    McGough, Doreen; Jardine, Lynne

    2017-01-01

    A number of published studies have suggested that high levels of exposure to manganese, especially those found in occupational settings, can adversely affect the reproductive system. The objective of this study was therefore to investigate if these findings can be replicated using the Sprague Dawley rat and, if so, to identify those parts of the reproductive system are more susceptible. Male and female rats were exposed to manganese dichloride (MnCl 2 ) via inhalation at concentrations of 0 (air-control); 5, 10 and 20μg/L air over 10 weeks (F0) and over 11 weeks (F1) prior to mating, and then throughout mating, gestation and lactation until termination after the F1 and F2 generation had reached Day 21 of lactation respectively. Animals were monitored for clinical signs of toxicity and for effects on body weight, food consumption, effects on the entire reproductive system including maternal care. The offspring were monitored for survival and growth up to weaning. Blood samples were taken from all adult animals for bioanalytical of manganese analysis prior to dosing, prior to mating and prior to weaning/necropsy. There were no deaths related to treatment, though respiratory tract effects were observed in F0 animals in the mid and high dose animals. Body weight and food consumption were affected at high dose in both generation. There were no treatment-related effects on the oestrous cycles, mating performance, sexual maturity, fertility or duration of gestation or litter size, the sperm motility, count of morphology (sperm) or the ovary follicle scoring in either generation. The No Observed Effect Level (NOEL) for reproductive performance was considered to be the target dose level of 20μg/L. Based on these findings, manganese chloride could not be considered a reprotoxicant under these conditions of exposure. Therefore, soluble and insoluble forms of inorganic manganese compounds by extrapolation cannot be considered as reprotoxicants. Copyright © 2016 Elsevier B

  11. Toxico-Neurological Effects of Piroxicam in Monogastric Animals

    Directory of Open Access Journals (Sweden)

    Saganuwan Alhaji Saganuwan

    2016-01-01

    Full Text Available Piroxicam is a benzothiazine compound with anti-inflammatory, antipyretic, and analgesic properties. Because of the very high efficacy of piroxicam and its increasing use in the treatment of carcinomas in dogs and cats, there is a need for acute toxicity study of piroxicam in monogastric animals and its potential for causing secondary poisoning in puppies. Piroxicam manufactured by Shanxi Federal Pharmaceutical Co, Ltd. was used for this study. Revised up-and-down procedure was used for the estimation of median lethal dose in mouse (259.4 ± 51.9 mg/kg, rat (259.4 ± 69.6 mg/kg, rabbit (707.5 ± 130.8 mg/kg, cat (437.5 ± 128.1 mg/kg, guinea pig (218.7 ± 64.1 mg/kg, monkey (733.3 ± 83.3 mg/kg, broiler (285.3 ± 62.5 mg/kg, hen (638.3 ± 115.4 mg/kg, turkey (707.5 ± 130.8 mg/kg, pigeon (375 ± 55.9 mg/kg, and duck (311.3 ± 46.6 mg/kg. The acute toxicity signs of piroxicam at doses 207.5 mg/kg and above observed in the animals are torticollis, opisthotonos, somnolence, lethargy, diarrhea, gastroenteritis, generalized internal bleeding, anemia, congestion of the lung and liver, flaccid paralysis, cheesy lung, urinary incontinence, engorged urinary bladder, convulsive jerking of the limbs, lying in ventral recumbency, gasping for air, roaring, and death. Three out of six puppies died after being fed the carcasses of poisoned turkey, duck, and hen administered piroxicam at doses of 1000, 415, and 1000 mg/kg, respectively. White flaky cheesy materials observed in turkeys were also observed in the gastrointestinal content of the puppies. Paleness of carcasses, watery crop content, dryness of pericardium, gastroenteritis, intestinal perforation, and whitish pericardium were observed in broilers. There were effusions in thoracic and abdominal cavities as seen in all other carcasses poisoned primarily by piroxicam. Administration of atropine (0.02 mg/kg led to survival of the remaining puppies. In conclusion, piroxicam is very to moderately toxic in

  12. Criticizing animal experimentation, at my peril.

    Science.gov (United States)

    Eisenman, Stephen F

    2016-01-01

    Initiatives leading to even modest reduction in animal use at major U.S. universities are likely to continue to face strong opposition. At least, that's the conclusion the author draws from his efforts at Northwestern University. In fact, despite a growing body of evidence that animal-based research is flawed at best and misleading or un-scientific at worst its use is growing at Northwestern and elsewhere. Moreover, recent discoveries concerning animal consciousness and emotion have not led to notable improvements in the conditions in which AWA protected animals live at the Chicago vivarium. There, animals languish in featureless rooms or sterile cages without access to daylight and with little opportunity to express their natural behaviors and aptitudes. The writer's public exposure of these conditions led to a fierce backlash. Unless there is a significant change in laboratory and university culture, change will only come when the marketplace and funding agencies demand better and more reliable, non-animal models for the testing of drug toxicity and effectiveness.

  13. Animal studies on growth and development.

    Science.gov (United States)

    Lerchl, Alexander

    2011-12-01

    Despite the fact that no plausible biological mechanism has yet been identified how electromagnetic fields below recommended exposure limits could negatively affect health of animals or humans, many experiments have been performed in various animal species, mainly mice and rats, to investigate the possible effects on growth and development. While older studies often suffered from sub-optimal exposure conditions, recent investigations, using sophisticated exposure devices and thus preventing thermal effects, have been performed without these limitations. In principle, two types of studies can be addressed: those which have investigated the carcinogenic or co-carcinogenic effects of exposure in developing animals, and those which have been done in developing animals without the focus on carcinogenic or co-carcinogenic effects. In both areas, the vast majority of publications did not show adverse effects. The largest study so far has been done in normal mice which have been chronically exposed to UMTS signals up to 1.3 W/kg SAR, thus 16 times higher than the whole-body exposure limit for humans. Even after four generations, no systematic or dose-dependent alterations in development or fertility could be found, supporting the view that negative effects on humans are very unlikely. Ongoing experiments in our laboratory investigate the effects of head-only exposure in rats (up to 10 W/kg local SAR) which are exposed from 14 days of age daily for 2 h. A battery of behavioral tests is performed in young, adult, and pre-senile animals. The results will help to clarify possible effects of exposure on brain development. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Inflammatory effects of the toxic cyanobacterium Geitlerinema amphibium.

    Science.gov (United States)

    Dogo, Camila Ranzatto; Bruni, Fernanda Miriane; Elias, Fabiana; Rangel, Marisa; Pantoja, Patricia Araujo; Sant'anna, Célia Leite; Lima, Carla; Lopes-Ferreira, Monica; de Carvalho, Luciana Retz

    2011-11-01

    Toxic cyanobacteria in public water reservoirs may cause severe health issues for livestock and human beings. Geitlerinema amphibium, which is frequently found in São Paulo City's drinking water supplies, showed toxicity in the standard mouse bioassay, while displaying signs of intoxication and post-mortem findings different from those showed by animals intoxicated by known cyanotoxins. We report here the alterations caused by G. amphibium methanolic extract on mouse microcirculatory network, as seen by in vivo intravital microscopy, besides observations on leukocyte migration, cytokine quantitation, and results of toxicological essays. Our data showed that G. amphibium methanolic extract displayed time- and dose-dependent pro-inflammatory activity, and that at lower doses [125 and 250 mg/kg body weight (b.w.)] increased the leukocyte rolling, caused partial venular stasis, as well as induced an increase in leukocyte counts in the peripheral blood and peritoneal washings. At higher doses (500 and 1000 mg/kg b.w.), the extract caused ischemic injury leading to animal death. As confirmed by mass spectrometric studies and polymyxin B test, the G. amphibium methanolic extract did not contain lipopolysaccharides. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Migration of nonylphenol from food-grade plastic is toxic to the coral reef fish species Pseudochromis fridmani.

    Science.gov (United States)

    Hamlin, Heather J; Marciano, Kathleen; Downs, Craig A

    2015-11-01

    Nonylphenol (NP) is a non-ionic surfactant used extensively in industrial applications, personal care products, and many plastics. We exposed marine orchid dottybacks (Pseudochromis fridmani) for 48h to either glass, Teflon, or two bags labeled as FDA food-grade polyethylene (PE1 and PE2) from different manufacturers. The PE2 bags leached high levels of NP into the contact water, which were taken up by the fish, and decreased short and long-term survival. Concentrations of NP that leached from the bags were consistent with 96h LC50 values determined in this study, indicating NP is the likely toxic agent. Despite being similarly labeled, the NP concentrations that leached from the bags and the resultant toxicity to the fish varied dramatically between manufacturers. This study highlights that some plastics, labeled as food-safe, can be highly toxic to aquatic animals, and could pose a greater threat to humans than previously realized. This study also highlights risks for aquatic animals exposed to increasing quantities of plastic waste. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. The paradox of human equivalent dose formula: A canonical case study of abrus precatorius aqueous leaf extract in monogastric animals

    Directory of Open Access Journals (Sweden)

    Saganuwan Alhaji Saganuwan

    2016-03-01

    Full Text Available There is abundant literature on the toxicity of A. precatorius seeds. However there is a need to define the toxicity limit of the Abrus precatorius leaf in monogastric animals. Human Equivalent Dose (HED which is equal to animal dose multiplied by animal km (metabolism constant divided by human km was used to project the LD50 of fifteen monogastric animals , where human km factor is body weight (kg divided by body surface area (m2. Human Equivalent No-observable Adverse Effect Doses were determined by multiplying the animal no-observable adverse effect dose by animal weight (Wa divided by human weight (Wh. The LD50 of the aqueous leaf extract of Abrus precatorius in mice was estimated to be between 2559.5 and 3123.3 mg/kg body weight. The LD50 extrapolated from mouse to rat (1349.3-1646.6 mg/kg, hamster (1855.3-2264.1 mg/kg, guinea pig (1279.5-1561.4 mg/kg, rabbit (618.4-754.7 mg/kg, monkey (593.7-724.5 mg/kg, cat (392.7-479.2 mg/kg, dog and baboon (371.1-452.8 mg/kg, child (297-362 mg/kg and adult human (197.8-241.5 mg/kg body weight respectively could be a reality. The therapeutic safe dose range for the animals was 1-12.5 mg/kg body weight for a period of 7 days, but at a dose (≤ 200 mg/kg body weight the leaf extract showed haematinic effect. However, at a higher dose (> 200 mg/kg, the extract showed haemolytic activity in rats, whereas at a dose (≥25.0 mg/kg, the leaf extract might be organotoxic in hamster, guinea pig, rabbit, monkey, cat, dog, baboon, child and adult human if administered orally for a period of 7 days.

  17. Toxicity and utilization of chemical weapons: does toxicity and venom utilization contribute to the formation of species communities?

    Science.gov (United States)

    Westermann, Fabian L; McPherson, Iain S; Jones, Tappey H; Milicich, Lesley; Lester, Philip J

    2015-08-01

    Toxicity and the utilization of venom are essential features in the ecology of many animal species and have been hypothesized to be important factors contributing to the assembly of communities through competitive interactions. Ants of the genus Monomorium utilize a variety of venom compositions, which have been reported to give them a competitive advantage. Here, we investigate two pairs of Monomorium species, which differ in the structural compositions of their venom and their co-occurrence patterns with the invasive Argentine ant. We looked at the effects of Monomorium venom toxicity, venom utilization, and aggressive physical interactions on Monomorium and Argentine ant survival rates during arena trials. The venom toxicity of the two species co-occurring with the invasive Argentine ants was found to be significantly higher than the toxicity of the two species which do not. There was no correlation between venom toxicity and Monomorium survival; however, three of the four Monomorium species displayed significant variability in their venom usage which was associated with the number of Argentine ant workers encountered during trials. Average Monomorium mortality varied significantly between species, and in Monomorium smithii and Monomorium antipodum, aggressive interactions with Argentine ants had a significant negative effect on their mortality. Our study demonstrates that different factors and strategies can contribute to the ability of a species to withstand the pressure of a dominant invader at high abundance, and venom chemistry appears to be only one of several strategies utilized.

  18. Two-generation reproductive toxicity study of implanted depleted uranium (DU) in CD rats.

    Science.gov (United States)

    Arfsten, D P; Still, K R; Wilfong, E R; Johnson, E W; McInturf, S M; Eggers, J S; Schaeffer, D J; Bekkedal, M Y-V

    2009-01-01

    Depleted uranium (DU) munitions and armor plating have been used in several conflicts over the last 17 yr, including the Persian Gulf War and the Iraq War. Because of its effectiveness and availability, DU will continue to be used in military applications into the foreseeable future. There is much controversy over the use of DU in weapons and equipment because of its potential radiological and toxic hazards, and there is concern over the chronic adverse health effects of embedded DU shrapnel in war veterans and bystanders. This study evaluated the effects of long-term implantation of DU on the reproductive success of F0 generation adults and development and survival of subsequent F1 and F2 generations in a two-generation reproductive toxicity study. F0 generation Sprague-Dawley rats, 8 wk of age, were surgically implanted with 0, 4, 8, 12, or 20 DU pellets (1 x 2 mm). Inert implant control animals were implanted with 12 or 20 tantallum (Ta) pellets. The F0 generation was then mated at 120 d post DU implantation. In the F0 generation, when measured on postimplantation d 27 and 117, uranium was present in the urine of DU-implanted animals in a dose-dependent manner. F0 reproductive success was similar across treatment groups and the maternal retrieval test revealed no changes in maternal behavior. DU implantation exerted no effect on the survival, health, or well-being of the F0 generation. Necropsy results of F0 animals were negative with the exception of a marked inflammatory response surrounding the implanted DU pellets. For the F1 generation, measures of F1 development through postnatal day (PND) 20 were unremarkable and no gross abnormalities were observed in F1 offspring. No uranium was detected in whole-body homogenates of PND 4 or PND 20 pups. Necropsy findings of F1 PND 20 pups were negative and no instances of ribcage malformation were observed in F1 PND 20 pups. Body weight and body weight gain of F1 rats through PND 120 were similar across treatment

  19. Rethinking developmental toxicity testing: Evolution or revolution?

    NARCIS (Netherlands)

    Scialli, Anthony R; Daston, George; Chen, Connie; Coder, Prägati S; Euling, Susan Y; Foreman, Jennifer; Hoberman, Alan M; Hui, Julia; Knudsen, Thomas; Makris, Susan L; Morford, LaRonda; Piersma, Aldert H; Stanislaus, Dinesh; Thompson, Kary E

    2018-01-01

    Current developmental toxicity testing adheres largely to protocols suggested in 1966 involving the administration of test compound to pregnant laboratory animals. After more than 50 years of embryo-fetal development testing, are we ready to consider a different approach to human developmental

  20. Animal studies on Spacelab-3

    Science.gov (United States)

    Schatte, C.; Grindeland, R.; Callahan, P.; Berry, W.; Funk, G.; Lencki, W.

    1987-01-01

    The flight of two squirrel monkeys and 24 rats on Spacelab-3 was the first mission to provide hands-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferom production by spleen cells, defective release of growth hormone by somatrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythropoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.

  1. Acute and subchronic toxicity studies of the original drug FS-1

    Directory of Open Access Journals (Sweden)

    Assem Kalykova

    2016-01-01

    Full Text Available Interest in iodine complexes has increased significantly in recent years because of their wide spectrum of biological activity. The FS-1 is an ion nanostructured complex formed by proteins and/or polypeptides, carbohydrates, salts of alkali and alkaline earth metals with intercalated iodine. Patented in 2014, it is intended for the treatment of infectious diseases of bacterial origin including nosocomial infections and multidrug resistant tuberculosis. The aim of the study was to determine its acute and subchronic toxicity. The study of acute and subchronic toxicity was performed on adult Wistar rats according to OECD guidelines. The data on acute toxicity showed LD50 > 2,000 mg/kg after a single intragastric administration. Twenty-eight days of FS-1 administration at a dose of 500 mg/kg resulted in toxic effects. At a dose of 250 mg/kg, the toxic effects were temporary and a return to normal followed after the recovery period. Doses of 100 mg/kg had no adverse effects on the rats.

  2. Studying Biotechnological Methods Using Animations: The Teacher's Role

    Science.gov (United States)

    Yarden, Hagit; Yarden, Anat

    2011-01-01

    Animation has great potential for improving the way people learn. A number of studies in different scientific disciplines have shown that instruction involving computer animations can facilitate the understanding of processes at the molecular level. However, using animation alone does not ensure learning. Students sometimes miss essential features…

  3. EFFECTS OF SILICON ON ALLEVIATING ARSENIC TOXICITY IN MAIZE PLANTS

    Directory of Open Access Journals (Sweden)

    Airon José da Silva

    2015-02-01

    Full Text Available Arsenic is a metalloid highly toxic to plants and animals, causing reduced plant growth and various health problems for humans and animals. Silicon, however, has excelled in alleviating stress caused by toxic elements in plants. The aim of this study was to investigate the effects of Si in alleviating As stress in maize plants grown in a nutrient solution and evaluate the potential of the spectral emission parameters and the red fluorescence (Fr and far-red fluorescence (FFr ratio obtained in analysis of chlorophyll fluorescence in determination of this interaction. An experiment was carried out in a nutrient solution containing a toxic rate of As (68 μmol L-1 and six increasing rates of Si (0, 0.25, 0.5, 1.0, 1.5, and 2.0 mmol L-1. Dry matter production and concentrations of As, Si, and photosynthetic pigments were then evaluated. Chlorophyll fluorescence was also measured throughout plant growth. Si has positive effects in alleviating As stress in maize plants, evidenced by the increase in photosynthetic pigments. Silicon application resulted in higher As levels in plant tissue; therefore, using Si for soil phytoremediation may be a promising choice. Chlorophyll fluorescence analysis proved to be a sensitive tool, and it can be successfully used in the study of the ameliorating effects of Si in plant protection, with the Fr/FFr ratio as the variable recommended for identification of temporal changes in plants.

  4. Toxicosis by Plant Alkaloids in Humans and Animals in Colombia

    Directory of Open Access Journals (Sweden)

    Gonzalo J. Diaz

    2015-12-01

    Full Text Available Due to its tropical location, chains of mountains, inter-Andean valleys, Amazon basin area, eastern plains and shores on both the Atlantic and Pacific Oceans, Colombia has many ecosystems and the second largest plant biodiversity in the world. Many plant species, both native and naturalized, are currently recognized as toxic for both animals and humans, and some of them are known to cause their toxic effects due to their alkaloid content. Among these, there are plants containing the hepatotoxic pyrrolizidine alkaloids, neurotoxins such as the indolizidine alkaloid swainsonine and the piperidine alkaloids coniine and γ-coniceine and tropane alkaloids. Unfortunately, the research in toxic plants in Colombia is not nearly proportional to its plant biodiversity and the scientific information available is only very scarce. The present review aims at summarizing the scarce information about plant alkaloid toxicosis in animals and humans in Colombia.

  5. Toxicosis by Plant Alkaloids in Humans and Animals in Colombia

    Science.gov (United States)

    Diaz, Gonzalo J.

    2015-01-01

    Due to its tropical location, chains of mountains, inter-Andean valleys, Amazon basin area, eastern plains and shores on both the Atlantic and Pacific Oceans, Colombia has many ecosystems and the second largest plant biodiversity in the world. Many plant species, both native and naturalized, are currently recognized as toxic for both animals and humans, and some of them are known to cause their toxic effects due to their alkaloid content. Among these, there are plants containing the hepatotoxic pyrrolizidine alkaloids, neurotoxins such as the indolizidine alkaloid swainsonine and the piperidine alkaloids coniine and γ-coniceine and tropane alkaloids. Unfortunately, the research in toxic plants in Colombia is not nearly proportional to its plant biodiversity and the scientific information available is only very scarce. The present review aims at summarizing the scarce information about plant alkaloid toxicosis in animals and humans in Colombia. PMID:26690479

  6. Developmental toxicity study in rats exposed dermally to clarified slurry oil for a limited period of gestation

    Energy Technology Data Exchange (ETDEWEB)

    Feuston, M.H.; Mackerer, C.R. [Stonybrook Laboratories, Inc., Princeton, NJ (United States)

    1996-10-11

    Clarified slurry oil (CSO, CAS number 64741-62-4), a refinery stream produced by processing crude oil, is a developmental toxicant when administered dermally throughout gestation to pregnant rats. The manifestations of developmental toxicity observed included embryolethlity and growth retardation; evidence of teratogenicity was limited, and not conclusive. The present study was undertaken to further explore the teratogenic potential of CSO. In an attempt to limit emnbryolethality and thereby promote detection of terata, CSO was administered once daily for a limited period of gestation i[gestation days (GD) 9-12], via dermal application, to pregnant Sprague-Dawley rats at doses of 0, 10, 100, and 1000 mg/kg. All animals were sacrificed on GD 20. Detailed examination of the dams was performed. Due to the screening nature of this investigation, fetal evaluations were limited to body weight measurements, external examinations, and evaluation of select visceral endpoints. In the dams exposed to CSO, significant decreases in body weight [absolute and gain (GD 9-13, GD 0-20)] and in the amount of food consumed were observed at 100 and 1000 mg/kg. Additional evidence of maternal toxicity observed at 1000 mg/kg included decreased absolute and relative thymus weights, increased absolute and relative liver weights, and aberrant serum chemistry. Ingestion of the test material was evident at the high dose. Developmental toxicity was observed at 1000 mg/kg and included increased embryolethality, decreased body weight, and anomalous development (cleft palate, brachydactyly, edema). Although a low incidence of abnormal fetal development was observed at 100 mg/kg, it was not conclusive that the alterations were due to CSO exposure. It is likely that three- to seven-ring polycyclic aromatic compounds present in CSO were responsible for the toxic effects observed. 33 refs., 5 tabs.

  7. What about animals dealing with working dogs, pets and other animals during terrorism incidents and disasters

    International Nuclear Information System (INIS)

    Eifried, G.

    2009-01-01

    It is highly likely that K9 teams (patrol, search and rescue, and cadaver) will be exposed to hazardous materials as a result of an act of CBRN terrorism, and thus require decontamination. Service animals and pets which have been exposed to toxic agents and materials will also need to be decontaminated, along with their owners. Emergency evacuation and sheltering plans need to consider how service animals, pets and livestock will be handled. The United States has recently made significant changes to focus in this regard, to the extent that caring for animals must now be addressed in disaster preparedness planning. In this paper we describe lessons learned from work done by the Massachusetts Urban Search and Rescue Team (USAR), and the response to hurricane Katrina, concerning the handling and decontamination of animals following major incidents. We discuss: how the new Federal and state mandates have changed evacuation and sheltering concepts; cooperation among government entities, veterinarians, animal facilities, humane societies, animal rescue organizations and animal owners; and describe some practical considerations and solutions to sheltering and mass decontamination of animals along with their humans.(author)

  8. Toxic properties of specific radiation determinant molecules, derived from radiated species

    Science.gov (United States)

    Popov, Dmitri; Maliev, Vecheslav; Kedar, Prasad; Casey, Rachael; Jones, Jeffrey

    Introduction: High doses of radiation induce the formation of radiation toxins in the organs of irradiated mammals. After whole body irradiation, cellular macromolecules and cell walls are damaged as a result of long-lived radiation-induced free radicals, reactive oxygen species, and fast, charged particles of radiation. High doses of radiation induce breaks in the chemical bonds of macromolecules and cross-linking reactions via chemically active processes. These processes result in the creation of novel modified macromolecules that possess specific toxic and antigenic properties defined by the type and dose of irradiation by which they are generated. Radiation toxins isolated from the lymph of irradiated animals are classified as hematotoxic, neurotoxic, and enteric non-bacterial (GI) radiation toxins, and they play an important role in the development of hematopoietic, cerebrovascular, and gastrointestinal acute radiation syndromes (ARS). Seven distinct toxins derived from post-irradiated animals have been designated as Specific Radiation Determinants (SRD): SRD-1 (neurotoxic radiation toxin generated by the cerebrovascular form of ARS), SRD-3 (enteric non-bacterial radiation toxins generated by the gastrointestinal form of ARS), and SRD-4 (hematotoxic radiation toxins generated by the hematological, bone marrow form of ARS). SRD-4 is further subdivided into four groups depending on the severity of the ARS induced: SRD-4/1, mild ARS; SRD-4/2, moderate ARS; SRD-4/3, severe ARS; and SRD-4/4, extremely severe ARS. The seventh SRD, SRD-2 is a toxic extract derived from animals suffering from a fourth form of ARS, as described in European literature and produces toxicity primarily in the autonimic nervous system. These radiation toxins have been shown to be responsible for the induction of important pathophysiological, immunological, and biochemical reactions in ARS. Materials and Methods: These studies incorporated the use of statistically significant numbers of a

  9. Assuring safety without animal testing: the case for the human testis in vitro.

    Science.gov (United States)

    Chapin, Robert E; Boekelheide, Kim; Cortvrindt, Rita; van Duursen, Majorie B M; Gant, Tim; Jegou, Bernard; Marczylo, Emma; van Pelt, Ans M M; Post, Janine N; Roelofs, Maarke J E; Schlatt, Stefan; Teerds, Katja J; Toppari, Jorma; Piersma, Aldert H

    2013-08-01

    From 15 to 17 June 2011, a dedicated workshop was held on the subject of in vitro models for mammalian spermatogenesis and their applications in toxicological hazard and risk assessment. The workshop was sponsored by the Dutch ASAT initiative (Assuring Safety without Animal Testing), which aims at promoting innovative approaches toward toxicological hazard and risk assessment on the basis of human and in vitro data, and replacement of animal studies. Participants addressed the state of the art regarding human and animal evidence for compound mediated testicular toxicity, reviewed existing alternative assay models, and brainstormed about future approaches, specifically considering tissue engineering. The workshop recognized the specific complexity of testicular function exemplified by dedicated cell types with distinct functionalities, as well as different cell compartments in terms of microenvironment and extracellular matrix components. This complexity hampers quick results in the realm of alternative models. Nevertheless, progress has been achieved in recent years, and innovative approaches in tissue engineering may open new avenues for mimicking testicular function in vitro. Although feasible, significant investment is deemed essential to be able to bring new ideas into practice in the laboratory. For the advancement of in vitro testicular toxicity testing, one of the most sensitive end points in regulatory reproductive toxicity testing, such an investment is highly desirable. Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  10. Resistance to organophosphorus agent toxicity in transgenic mice expressing the G117H mutant of human butyrylcholinesterase

    International Nuclear Information System (INIS)

    Wang Yuxia; Ticu Boeck, Andreea; Duysen, Ellen G.; Van Keuren, Margaret; Saunders, Thomas L.; Lockridge, Oksana

    2004-01-01

    Organophosphorus toxicants (OP) include chemical nerve agents and pesticides. The goal of this work was to find out whether an animal could be made resistant to OP toxicity by genetic engineering. The human butyrylcholinesterase (BChE) mutant G117H was chosen for study because it has the unusual ability to hydrolyze OP as well as acetylcholine, and it is resistant to inhibition by OP. Human G117H BChE, under the control of the ROSA26 promoter, was expressed in all tissues of transgenic mice. A stable transgenic mouse line expressed 0.5 μg/ml of human G117H BChE in plasma as well as 2 μg/ml of wild-type mouse BChE. Intestine, kidneys, stomach, lungs, heart, spleen, liver, brain, and muscle expressed 0.6-0.15 μg/g of G117H BChE. Transgenic mice were normal in behavior and fertility. The LD50 dose of echothiophate for wild-type mice was 0.1 mg/kg sc. This dose caused severe cholinergic signs of toxicity and lethality in wild-type mice, but caused no deaths and only mild toxicity in transgenic animals. The mechanism of protection was investigated by measuring acetylcholinesterase (AChE) and BChE activity. It was found that AChE and endogenous BChE were inhibited to the same extent in echothiophate-treated wild type and transgenic mice. This led to the hypothesis that protection against echothiophate toxicity was not explained by hydrolysis of echothiophate. In conclusion, the transgenic G117H BChE mouse demonstrates the factors required to achieve protection from OP toxicity in a vertebrate animal

  11. Chronic toxicity/carcinogenicity studies of FD & C Yellow No. 5 (tartrazine) in rats.

    Science.gov (United States)

    Borzelleca, J F; Hallagan, J B

    1988-03-01

    FD & C Yellow No. 5 was fed to Charles River CD rats as a dietary admixture in two long-term toxicity/carcinogenicity studies. The studies were conducted with an in utero phase in which the compound was administered to the F0 generation rats (60/sex/group) at levels of 0.0, 0.0, 0.1, 1.0 or 2.0% ('original study') and 0.0 or 5.0% ('high-dose study'). The concurrent control groups received the basal diet. After random selection of the F1 animals, the long-term phase was initiated using the same dietary levels with 70 rats of each sex/group, including the three control groups. The maximum exposure to the colouring was 113 and 114 wk for males and females, respectively, in the 'original' study and 122 and 125 wk for males and females, respectively, in the 'high-dose' study. No compound-related effects were noted. The no-adverse-effect level found in this study was 5.0% in the diet providing an average intake of 2641 and 3348 mg/kg/day for male and female rats, respectively.

  12. Toxicity of ozone and nitrogen dioxide to alveolar macrophages: comparative study revealing differences in their mechanism of toxic action

    NARCIS (Netherlands)

    Rietjens, I. M.; Poelen, M. C.; Hempenius, R. A.; Gijbels, M. J.; Alink, G. M.

    1986-01-01

    The toxicity of ozone and nitrogen dioxide is generally ascribed to their oxidative potential. In this study their toxic mechanism of action was compared using an intact cell model. Rat alveolar macrophages were exposed by means of gas diffusion through a Teflon film. In this in vitro system, ozone

  13. Modulation of aflatoxin toxicity and biomarkers by lycopene in F344 rats

    International Nuclear Information System (INIS)

    Tang, Lili; Guan Hongxia; Ding Xiaolin; Wang Jiasheng

    2007-01-01

    Modulation by lycopene of aflatoxin B 1 (AFB 1 )-induced toxic effects, metabolism, and metabolic activations was studied in young F344 rats. Animals were pretreated orally with either corn oil (control group) or lycopene [100 mg/kg body weight (b.w.), intervention group] 5 days/week for 2 weeks. Control animals were then treated daily with AFB 1 (250 μg/kg b.w) alone. Intervention animals were administered lycopene (100 mg/kg b.w.) at 1 h following a daily treatment with AFB 1 (250 μg/kg b.w.). Pretreatment and intervention with lycopene significantly reduced the toxic effect caused by AFB 1 and greatly modulated AFB 1 metabolism and metabolic activation. Urinary excretion of AFB 1 phase 1 metabolites, AFM 1 , AFQ 1 , and AFP 1 , was significantly decreased in lycopene-treated animals. Formation of serum AFB 1 -albumin adducts was also significantly reduced. The rate of reduction was from approximately 30% on day 1 (p 1 -DNA adducts in liver compared to control animals, with the highest reduction (52.7%) occurring on day 3 (p 1 -N 7 -guanine excreted in urine were also significantly decreased. Urinary excretion of the phase 2 detoxification metabolite, AFB 1 -mecapturic acid, was significantly increased in lycopene-intervened animals. AFB 1 -induced urinary excretion of 8-hydroxydeoxyguanosine was also reduced to 50% on day 7 after lycopene intervention. Collectively, these results suggest that inhibition of phase 1 metabolism and metabolic activation, as well as induction of phase 2 detoxification enzyme activity are the potential mechanisms for the chemopreventive effects of lycopene

  14. Past, present and emerging toxicity issues for jet fuel.

    Science.gov (United States)

    Mattie, David R; Sterner, Teresa R

    2011-07-15

    The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8 and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Past, present and emerging toxicity issues for jet fuel

    International Nuclear Information System (INIS)

    Mattie, David R.; Sterner, Teresa R.

    2011-01-01

    The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8 and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels.

  16. 40 CFR 799.9355 - TSCA reproduction/developmental toxicity screening test.

    Science.gov (United States)

    2010-07-01

    ... developmental defects should not be used. Healthy virgin animals, not subjected to previous experimental..., except legal holidays. (1) OECD (1995). Reproduction/Developmental Toxicity Screening Test, OECD 421...

  17. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop

    Science.gov (United States)

    Since the 1940’s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that ...

  18. Thyroid cancer in toxic and non-toxic multinodular goiter

    Directory of Open Access Journals (Sweden)

    Cerci C

    2007-01-01

    Full Text Available Background : Many authors have claimed that hyperthyroidism protects against thyroid cancer and believed that the incidence of malignancy is lower in patients with toxic multinodular goiter (TMG than in those with non-toxic multinodular goiter. But in recent studies, it was reported that the incidence of malignancy with TMG is not as low as previously thought. Aim : To compare the thyroid cancer incidence in patients with toxic and non-toxic multinodular goiter. Settings and Design : Histology reports of patients treated surgically with a preoperative diagnosis of toxic and non-toxic multinodular goiter were reviewed to identify the thyroid cancer incidence. Patients having a history of neck irradiation or radioactive iodine therapy were excluded from the study. Materials and Methods : We reviewed 294 patients operated between 2001-2005 from toxic and non-toxic multinodular goiter. One hundred and twenty-four of them were toxic and 170 were non-toxic. Hyperthyroidism was diagnosed by elevated tri-iodothyroinine / thyroxine ratios and low thyroid-stimulating hormone with clinical signs and symptoms. All patients were evaluated with ultrasonography and scintigraphy and fine needle aspiration biopsy. Statistical Analysis Used : Significance of the various parameters was calculated by using ANOVA test. Results : The incidence of malignancy was 9% in the toxic and 10.58% in the non-toxic multinodular goiter group. Any significant difference in the incidence of cancer and tumor size between the two groups could not be detected. Conclusions : The incidence of malignancy in toxic multinodular goiter is not very low as thought earlier and is nearly the same in non-toxic multinodular goiter.

  19. Towards Global QSAR Model Building for Acute Toxicity: Munro Database Case Study

    Directory of Open Access Journals (Sweden)

    Swapnil Chavan

    2014-10-01

    Full Text Available A series of 436 Munro database chemicals were studied with respect to their corresponding experimental LD50 values to investigate the possibility of establishing a global QSAR model for acute toxicity. Dragon molecular descriptors were used for the QSAR model development and genetic algorithms were used to select descriptors better correlated with toxicity data. Toxic values were discretized in a qualitative class on the basis of the Globally Harmonized Scheme: the 436 chemicals were divided into 3 classes based on their experimental LD50 values: highly toxic, intermediate toxic and low to non-toxic. The k-nearest neighbor (k-NN classification method was calibrated on 25 molecular descriptors and gave a non-error rate (NER equal to 0.66 and 0.57 for internal and external prediction sets, respectively. Even if the classification performances are not optimal, the subsequent analysis of the selected descriptors and their relationship with toxicity levels constitute a step towards the development of a global QSAR model for acute toxicity.

  20. Environment-friendly approach for the removal of toxic metals

    International Nuclear Information System (INIS)

    Zahra, N.; Mehmood, F.; Sheikh, S.T.; Javed, K.; Amin, A.

    2006-01-01

    Water pollution is serious economical problem and the presence of toxic metals like lead causes contamination of plants and then through nutritional chain it affects the health of humans and animals. This research work describes the removal of lead from wastewater using natural bentonites taken from various areas of Pakistan. The batch adsorption process was applied to remove this toxic metal. The quantities of lead metal before and after the treatment of standard solutions with different samples of bentonite were determined by atomic absorption spectroscopic method. The studies were carried out at room temperature, pH 7 and -200 mesh particle size using 50 ml of metal solutions. The time taken to maintain equilibrium was one hour. Then percentage adsorption was estimated on bentonite samples. (author)

  1. Human health effects associated with exposure to toxic Cyanobacteria – what is the evidence?

    Science.gov (United States)

    Reports of toxic cyanobacteria blooms are increasing worldwide, as warming water and eutrophic surface water systems support the development of blooms. As awareness of toxic cyanobacteria blooms increases, reports of associated human and animal illnesses have also increased, but ...

  2. Biological toxicity evaluation of Hanford Site waste grouts

    International Nuclear Information System (INIS)

    Rebagay, T.V. Dodd, D.A.; Voogd, J.A.

    1992-10-01

    Liquid wastes containing radioactive, hazardous, and regulated chemicals have been generated throughout the 50 years of operation of the Hanford Site of the US Department of Energy near Richland, Washington. These wastes are currently stored onsite in single- and double-shell carbon steel tanks. To effectively handle and treat these wastes, their degree of toxicity must be determined. The disposal of the low-level radioactive liquid portion of the wastes involves mixing the wastes with pozzolanic blends to form grout. Potential environmental hazards posed by grouts are largely unknown. Biological evaluation of grout toxicity is needed to provide information on the potential risks of animal and plant exposure to the grouts. The fish, rat, and Microtox toxicity tests described herein indicate that the grouts formed from Formulations I and 2 are nonhazardous and nondangerous. Using the Microtox solid-phase protocol, both soluble and insoluble organic and inorganic toxicants in the grouts can be detected. This protocol may be used for rapid screening of environmental pollutants and toxicants

  3. Rapid bioassay-guided screening of toxic substances in vegetable oils that shorten the life of SHRSP rats

    Directory of Open Access Journals (Sweden)

    Lewandowski Paul

    2010-02-01

    Full Text Available Abstract It has been consistently reported that vegetable oils including canola oil have a life shortening effect in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP and this toxic effect is not due to the fatty acid composition of the oil. Although it is possible that the phytosterol content or type of phytosterol present in vegetable oils may play some role in the life shortening effect observed in SHRSP rats this is still not completely resolved. Furthermore supercritical CO2 fractionation of canola oil with subsequent testing in SHRSP rats identified safe and toxic fractions however, the compounds responsible for life shortening effect were not characterised. The conventional approach to screen toxic substances in oils using rats takes more than six months and involves large number of animals. In this article we describe how rapid bioassay-guided screening could be used to identify toxic substances derived from vegetable oils and/or processed foods fortified with vegetable oils. The technique incorporates sequential fractionation of oils/processed foods and subsequent treatment of human cell lines that can be used in place of animal studies to determine cytotoxicity of the fractions with structural elucidation of compounds of interest determined via HPLC-MS and GC-MS. The rapid bioassay-guided screening proposed would require two weeks to test multiple fractions from oils, compared with six months if animal experiments were used to screen toxic effects. Fractionation of oil before bio-assay enhances the effectiveness of the detection of active compounds as fractionation increases the relative concentration of minor components.

  4. Working in partnership to advance the 3Rs in toxicity testing

    International Nuclear Information System (INIS)

    Holmes, Anthony M.; Creton, Stuart; Chapman, Kathryn

    2010-01-01

    Toxicological assessment of pharmaceutical and non-pharmaceutical chemicals is a regulatory requirement to ensure all compounds likely to be exposed to humans or the environment are safe. These studies rely on the use of large numbers of animals and involve a number of assumptions and extrapolations that remain controversial in assuring consumer safety. The UK's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) has taken a collaborative approach to identify opportunities for implementation of the 3Rs principles (Replacement, Reduction and Refinement) to drive innovation and support animal welfare in toxicity testing. This review highlights the mechanisms by which the NC3Rs is working with the pharmaceutical and chemical industries and regulatory authorities to achieve these goals.

  5. Get the lead out: Wildlife advocates file suit to replace toxic ammo ...

    African Journals Online (AJOL)

    2007-03-02

    Mar 2, 2007 ... Get the lead out: Wildlife advocates file suit to replace toxic ammo with safer alternatives. Simple, practical ... who eats game, which often contains shot or small metal fragments. Lead is an extremely toxic ... eating meat from animals taken with lead ammunition often have unhealthy lead levels in their own ...

  6. Impacts of cereal ergot in food animal production

    Directory of Open Access Journals (Sweden)

    Stephanie eCoufal-Majewski

    2016-02-01

    Full Text Available The negative impacts of ergot contamination of grain on the health of humans and animals were first documented during the 5th century AD. Although ergotism is now rare in humans, cleaning contaminated grain concentrates ergot bodies in screenings which are used as livestock feed. Ergot is found worldwide, with even low concentrations of alkaloids in the diet (<100 ppb total reducing the growth efficiency of livestock. Extended periods of increased moisture and cold during flowering promote the development of ergot in cereal crops. Furthermore, the unpredictability of climate change may have detrimental impacts to important cereal crops such as wheat, barley and rye, favouring ergot production. Allowable limits for ergot in livestock feed are confusing as they may be determined by proportions of ergot bodies or by total levels of alkaloids, measurements which may differ widely in their estimation of toxicity. The proportion of individual alkaloids including ergotamine, ergocristine, ergosine, ergocornine and ergocryptine is extremely variable within ergot bodies and the relative toxicity of these alkaloids has yet to be determined. This raises concerns that current recommendations on safe levels of ergot in feeds may be unreliable. Furthermore, the total ergot alkaloid content is greatly dependent on the geographic region, harvest year, cereal species, variety and genotype. Considerable animal to animal variation in the ability of the liver to detoxify ergot alkaloids also exists and the impacts of factors such as pelleting of feeds or use of binders to reduce bioavailability of alkaloids require study. Accordingly, unknowns greatly outnumber the knowns for cereal ergot and further study to help better define allowable limits for livestock would be welcome.

  7. The use of GRADE approach in systematic reviews of animal studies.

    Science.gov (United States)

    Wei, Dang; Tang, Kun; Wang, Qi; Estill, Janne; Yao, Liang; Wang, Xiaoqin; Chen, Yaolong; Yang, Kehu

    2016-03-15

    The application of GRADE (Grading of Recommendations Assessment, Development and Evaluation) in SR of animal studies can promote the translation from bench to bedside. We aim to explore the use of GRADE in systematic reviews of animal studies. We used a theoretical analysis method to explore the use of GRADE in SR of animal studies and applied in a SR of animal studies. Meanwhile, we presented and discussed our results in two international conferences. Five downgrade factors were considered as follows in systematic reviews of animal studies: 1) Risk of bias: the SYRCLE tool can be used for assessing the risk of bias of animal studies. 2) Indirectness: we can assess indirectness in systematic reviews of animal studies from the PICO. 3) Inconsistency: similarity of point estimates, extent of overlap of confidence intervals and statistical heterogeneity are also suitable to evaluate inconsistency of evidence from animal studies. 4) Imprecision: optimal information size (OIS) and 95% confidence intervals (CIs) are also suitable for systematic reviews of animal studies, like those of clinical trials. 5) Publication bias: we need to consider publication bias comprehensively through the qualitative and quantitative methods. The methods about the use of GRADE in systematic review of animal studies are explicit. However, the principle about GRADE in developing the policy based on the evidence from animal studies when there is an emergency of public health. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. Toxicity evaluation of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) polymeric micelles following multiple oral and intraperitoneal administration to rats.

    Science.gov (United States)

    Binkhathlan, Ziyad; Qamar, Wajhul; Ali, Raisuddin; Kfoury, Hala; Alghonaim, Mohammed

    2017-09-01

    Methoxy poly(ethylene oxide)- block -poly(ɛ-caprolactone) (PEO- b -PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO- b -PCL block copolymers and assess the toxic effects of drug-free PEO- b -PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO- b -PCL micelles, sixty animals were divided into two major groups: The first group received PEO- b -PCL micelles (100 mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

  9. Toxicity evaluation of methoxy poly(ethylene oxide-block-poly(ε-caprolactone polymeric micelles following multiple oral and intraperitoneal administration to rats

    Directory of Open Access Journals (Sweden)

    Ziyad Binkhathlan

    2017-09-01

    Full Text Available Methoxy poly(ethylene oxide-block-poly(ɛ-caprolactone (PEO-b-PCL copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO-b-PCL block copolymers and assess the toxic effects of drug-free PEO-b-PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO-b-PCL micelles, sixty animals were divided into two major groups: The first group received PEO-b-PCL micelles (100 mg/kg by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

  10. Effects of SO/sub 2/ or NOx on toxic and genotoxic properties of chemical carcinogens. II. Short term in vivo studies

    Energy Technology Data Exchange (ETDEWEB)

    Pool, B L; Brendler, S; Klein, R G; Monarca, S; Pasquini, R; Schmezer, P; Zeller, W J

    1988-07-01

    Short term in vivo studies were performed to study biological effects of the common air pollutants SO2 or NOx and their influence on the genotoxic activities of nitrosamines. Hepatocytes and lung cells were isolated from Sprague-Dawley rats which had inhaled 50 p.p.m. of SO2 or NOx for 2 weeks. After incubating the cells for 1 h, genotoxicity was determined in hepatocytes by measuring DNA single-strand breaks induced by N-nitroso-acetoxymethylmethylamine, N-nitrosodimethylamine and N-nitrosomethylbenzylamine. Parameters of toxicity (trypan blue exclusion and leakage of serum enzymes) were determined in both liver and lung cells also following 1 h incubation. The activities of aryl hydrocarbon hydroxylase (AHH), nitrosodimethylamine demethylase (NDMA-D) and glutathione-S-transferase (GST) were determined in subcellular microsomal fractions isolated from lung and liver tissues. Finally, as a measure of overall toxicity, the activities of various serum enzymes were determined in the blood serum of the rats. It was found that the induction of DNA single-strand breaks by three nitrosamines was decreased in hepatocytes from SO2-treated animals. The viability of rat hepatocytes and of rat lung cells, as determined by trypan blue exclusion, was similar in all three treatment groups immediately after isolation, as well as after 1 h incubation with DMSO or with the nitrosamines. In contrast, the leakage of enzymes was different in hepatocytes of SO2-treated rats, since lactate dehydrogenase activity was decreased. Leakage of enzymes from the lung cells did not differ from group to group, but was lower than from hepatocytes. Foreign compound metabolizing enzymes were mainly decreased in NOx-treated animals, namely AHH, NDMA-D and GST in liver and GST in the lung. For SO2-treated animals NDMA-D was increased in liver and GST was decreased in lung.

  11. Acute, subacute and subchronic toxicological studies of carissa carandas leaves (ethanol extract): a plant active against cardiovascular diseases

    International Nuclear Information System (INIS)

    Shamim, S.

    2014-01-01

    The Purpose of this research study was to examine the toxicological effects of aqueous: ethanol (1:1) extract of Carissa carandas leaves extracts in rats. Methodolgy: Acute toxicity studies were conducted to check the LD50 values in experimental animals. Autopsy after acute toxicity revealed that no gross changes were observed in organs like liver, spleen, heart and kidney among the animals of group N (control) and S (treated). The appearance of organs of Group S animals was comparable with that of Group N animals. Results: No signs of toxicity and mortality were observed in treated group after sub acute toxicity as compared to the control group. The histopathological studies after subchronic toxicity in doses of 1750 mg/kg (p.o.) and 5000 mg/kg (p.o) showed no toxic effects on organs like liver, heart, kidney and spleen. While chronic toxicity in dose 5000 mg/kg (p.o.) showed some histological changes. (author)

  12. Vermicomposting eliminates the toxicity of Lantana (Lantana camara) and turns it into a plant friendly organic fertilizer

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, N.; Abbasi, Tasneem; Abbasi, S.A., E-mail: prof.s.a.abbasi@gmail.com

    2015-11-15

    Highlights: • It is shown for the first time that Lantana can lose its toxicity when vermicomposted. • The Lantana vermicompost is shown to be a good organic fertilizer. • FTIR studies identified Lantana’s toxic constituents destroyed by vermicomposting. • The findings have far-reaching implications in the gainful use of harmful weeds. - Abstract: In evidently the first study of its kind, vermicompost derived solely from a weed known to possess plant and animal toxicity was used to assess its impact on the germination and early growth of several plant species. No pre-composting or supplementation of animal manure was done to generate the vermicompost in order to ensure that the impact is clearly attributable to the weed. Whereas the weed used in this study, Lantana (Lantana camara), is known to possess strong negative allelopathy, besides plant/animal toxicity in other forms, its vermicompost was seen to be a good organic fertilizer as it increased germination success and encouraged growth of all the three botanical species explored by the authors – green gram (Vigna radiata), ladies finger (Abelmoschus esculentus) and cucumber (Cucumis sativus). In terms of several physical, chemical and biochemical attributes that were studied, the vermicompost appeared plant-friendly, giving best results in general when employed at concentrations of 1.5% in soil (w/w). Fourier transform infrared spectrometry revealed that the phenols and the sesquiterpene lactones that are responsible for the allelopathic impact of Lantana were largely destroyed in the course of vermicomposting. There is also an indication that lignin content of Lantana was reduced during its vermicomposting. The findings open up the possibility that the billions of tons of phytomass that is generated annually by Lantana and other invasives can be gainfully utilized in generating organic fertilizer via vermicomposting.

  13. Vermicomposting eliminates the toxicity of Lantana (Lantana camara) and turns it into a plant friendly organic fertilizer

    International Nuclear Information System (INIS)

    Hussain, N.; Abbasi, Tasneem; Abbasi, S.A.

    2015-01-01

    Highlights: • It is shown for the first time that Lantana can lose its toxicity when vermicomposted. • The Lantana vermicompost is shown to be a good organic fertilizer. • FTIR studies identified Lantana’s toxic constituents destroyed by vermicomposting. • The findings have far-reaching implications in the gainful use of harmful weeds. - Abstract: In evidently the first study of its kind, vermicompost derived solely from a weed known to possess plant and animal toxicity was used to assess its impact on the germination and early growth of several plant species. No pre-composting or supplementation of animal manure was done to generate the vermicompost in order to ensure that the impact is clearly attributable to the weed. Whereas the weed used in this study, Lantana (Lantana camara), is known to possess strong negative allelopathy, besides plant/animal toxicity in other forms, its vermicompost was seen to be a good organic fertilizer as it increased germination success and encouraged growth of all the three botanical species explored by the authors – green gram (Vigna radiata), ladies finger (Abelmoschus esculentus) and cucumber (Cucumis sativus). In terms of several physical, chemical and biochemical attributes that were studied, the vermicompost appeared plant-friendly, giving best results in general when employed at concentrations of 1.5% in soil (w/w). Fourier transform infrared spectrometry revealed that the phenols and the sesquiterpene lactones that are responsible for the allelopathic impact of Lantana were largely destroyed in the course of vermicomposting. There is also an indication that lignin content of Lantana was reduced during its vermicomposting. The findings open up the possibility that the billions of tons of phytomass that is generated annually by Lantana and other invasives can be gainfully utilized in generating organic fertilizer via vermicomposting

  14. Study of analgesic activity of ethanol extract of Phlogacanthus thyrsiflorus on experimental animal models

    Directory of Open Access Journals (Sweden)

    Apurba Mukherjee

    2009-06-01

    Full Text Available The aim of the study was to evaluate the central and peripheral analgesic action of Phlogacanthus thyrsiflorus in experimental animal models. The extract was prepared by percolation method and acute oral toxicity testing was performed as per OECD guidelines. Analgesic activity was assessed by tail flick method (for central action and glacial acetic acid-induced writhing test (for peripheral action. Leaves extract (500 mg/kg, p.o. and aspirin (100 mg/kg showed significant peripheral analgesic activity (p<0.05. Leaves extract (500 mg/kg, p.o. and pethidine (50 mg/kg, i.p. also showed significant central analgesic activity (p<0.05. Naloxone (1 mg/kg, s.c. was used to find the mechanism of central analgesic action. Some partial agonistic activity for the opioid receptors seems to be probable mechanism of action.

  15. 78 FR 37176 - Addition of Nonylphenol Category; Community Right-to-Know Toxic Chemical Release Reporting

    Science.gov (United States)

    2013-06-20

    ... species of marine animals; the blue mussel (Mytilus edulis), the three-spined stickleback fish...., A. Bergman, A. Granmo, and M. Berggren. 1990. Bioaccumulation of 4-nonylphenol in marine animals--A... previously peer reviewed (Ref. 3). A. Acute Toxicity to Aquatic Animals 1. Freshwater Species. The acute...

  16. Green Tea Protects Testes against Atrazine-induced Toxicity in Rat

    Directory of Open Access Journals (Sweden)

    Reza Kheirandish

    2017-06-01

    Full Text Available Background: Atrazine (ATZ is a common herbicide in agriculture for control of grass and broad-leaved weeds. It persists in the environment and causes reproductive problems in both human and animals. The present study was aimed at protective effect of green tea against ATZ toxicity in the reproductive system of male rats. Methods: The present study was performed in Veterinary School, Shahid Bahonar University of Kerman in 2016. ATZ and treatment groups received ATZ daily 200 mg/kg BW orally for 14 d. In addition, 0.2% methanolic green tea extract was administrated in the treatment group. Results: In histopathologic investigation, number of germinal layers reduced in the most seminiferous tubules in the ATZ group and spermatids were absence. Necrotic spermatocytes, spermatids, and spermatozoa were evident in the testicular tubules. In the morphometric measurements, tubular diameter, germinal epithelium height, and meiosis index decreased significantly. Conclusion: Green tea extract had reduced testicular toxicity of atrazine significantly. ATZ induces toxicity through oxidative damage and green tea extract can protect the testes due to antioxidant activity of its polyphenols especially flavonoids.

  17. Blood Parameters and Toxicity of Chromium Picolinate Oral Supplementation in Lambs.

    Science.gov (United States)

    Dallago, Bruno Stéfano Lima; Braz, ShélidaVasconcelos; Marçola, Tatiana Guerrero; McManus, Concepta; Caldeira, Denise Ferreira; Campeche, Aline; Gomes, Edgard Franco; Paim, Tiago Prado; Borges, Bárbara Oliveira; Louvandini, Helder

    2015-11-01

    The effects of oral supplementation of chromium picolinate (CrPic) on various blood parameters and their possible toxicity on the liver, kidneys, lungs, heart, and testis were investigated. Twenty-four Santa Inês (SI) lambs were treated with four different concentrations of CrPic (six animals/treatment): placebo, 0.250, 0.375, and 0.500 mg CrPic/animal/day for 84 days. The basal diet consisted of hay Panicum maximum cv Massai and concentrate. Blood and serum were collected fortnightly for analysis. On day 84, the animals were euthanized, and histopathological analysis in the liver, kidney, heart, lung, and testis was made. The liver and kidney were also submitted to electronic microscopy analysis. Differences between treatments (P plasm protein (day 56 and day 84), and triglycerides (day 70). There was no statistically significant relationship between Cr supplementation and histopathology findings, although some animals treated with supplementary Cr showed morphological changes in the liver, kidney, and testis. Thus, the effectiveness of supplementation with Cr remains in doubt as to its physiological action and toxicity in sheep.

  18. Enrofloxacin: pharmacokinetics and metabolism in domestic animal species.

    Science.gov (United States)

    López-Cadenas, Cristina; Sierra-Vega, Matilde; García-Vieitez, Juan J; Diez-Liébana, M José; Sahagún-Prieto, Ana; Fernández-Martínez, Nélida

    2013-12-01

    Enrofloxacin is a fluorquinolone exclusively developed for use in veterinary medicine (1980). The kinetics of enrofloxacin are characterized, in general terms, by high bioavailability in most species and rapid absorption after IM, SC or oral administration. However, several studies reported that enrofloxacin showed low bioavailability after oral administration in ruminants. This drug has a broad distribution in the organism, excellent tissue penetration and long serum half-life. Also, enrofloxacin is characterized by a low host toxicity, a broad antibacterial spectrum and high bactericidal activity against major pathogenic bacteria (both Gram-positive and Gram-negative), and intracellular organisms found in diseased animals. The kinetics vary according to the route of administration, formulation, animal species, age, body condition, and physiological status, all of which contribute to differences in drug efficacy. The pharmacokinetic properties of drugs are closely related to their pharmacological efficiency, so it is important to know their behavior in each species that is used. This article reviews the pharmacokinetics of enrofloxacin in several domestic animal species.

  19. Improvement in Shrimp Hatchery Procedures for Toxicity Tests

    International Nuclear Information System (INIS)

    Nor Azizah Marsiddi; Fazliana Mohd Saaya; Anee Suryani Sued

    2015-01-01

    Toxicity testing of brine shrimp Artemia salina Brine shrimp lethality assay is a screening test to determine half the dose mortality (LC50) for its shrimp given certain herbal extract at a concentration tested. The shrimp child mortality half a dose indicator to determine level of toxicity before further testing done on animal cell culture and animal experiments also on the mouse. The use of new hardware, namely Artemio 1 has increased its shrimp production at a rate that more and faster than the use of the black box hatching previously taken from the method by Solis, 1993. brine shrimp eggs from Artemio mix also easier to use because it contains egg and sea salt have been ready mixed for use in experiments. In conclusion, this method improvements help increase the number of offspring produced shrimp and produce experimental method easier than previous methods. (author)

  20. Hibiscus sabdariffa L. in the treatment of hypertension and hyperlipidemia: a comprehensive review of animal and human studies.

    Science.gov (United States)

    Hopkins, Allison L; Lamm, Marnie G; Funk, Janet L; Ritenbaugh, Cheryl

    2013-03-01

    The effectiveness of Hibiscus sabdariffa L. (HS) in the treatment of risk factors associated with cardiovascular disease is assessed in this review by taking a comprehensive approach to interpreting the randomized clinical trial (RCT) results in the context of the available ethnomedical, phytochemical, pharmacological, and safety and toxicity information. HS decoctions and infusions of calyxes, and on occasion leaves, are used in at least 10 countries worldwide in the treatment of hypertension and hyperlipidemia with no reported adverse events or side effects. HS extracts have a low degree of toxicity with a LD50 ranging from 2,000 to over 5,000mg/kg/day. There is no evidence of hepatic or renal toxicity as the result of HS extract consumption, except for possible adverse hepatic effects at high doses. There is evidence that HS acts as a diuretic, however in most cases the extract did not significantly influence electrolyte levels. Animal studies have consistently shown that consumption of HS extract reduces blood pressure in a dose dependent manner. In RCTs, the daily consumption of a tea or extract produced from HS calyxes significantly lowered systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults with pre to moderate essential hypertension and type 2 diabetes. In addition, HS tea was as effective at lowering blood pressure as the commonly used blood pressure medication Captropril, but less effective than Lisinopril. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides were lowered in the majority of normolipidemic, hyperlipidemic, and diabetic animal models, whereas high-density lipoprotein cholesterol (HDL-C) was generally not affected by the consumption of HS extract. Over half of the RCTs showed that daily consumption of HS tea or extracts had favorable influence on lipid profiles including reduced total cholesterol, LDL-C, triglycerides, as well as increased HDL-C. Anthocyanins found in abundance in HS

  1. Hibiscus sabdariffa L. in the treatment of hypertension and hyperlipidemia: a comprehensive review of animal and human studies

    Science.gov (United States)

    Hopkins, Allison L.; Lamm, Marnie G.; Funk, Janet; Ritenbaugh, Cheryl

    2013-01-01

    The effectiveness of Hibiscus sabdariffa L. (HS) in the treatment of risk factors associated with cardiovascular disease is assessed in this review by taking a comprehensive approach to interpreting the randomized clinical trial (RCT) results in the context of the available ethnomedical, phytochemical, pharmacological, and safety and toxicity information. HS decoctions and infusions of calyxes, and on occasion leaves, are used in at least 10 countries worldwide in the treatment of hypertension and hyperlipidemia with no reported adverse events or side effects. HS extracts have a low degree of toxicity with a LD50 ranging from 2,000 to over 5,000 mg/kg/day. There is no evidence of hepatic or renal toxicity as the result of HS extract consumption, except for possible adverse hepatic effects at high doses. There is evidence that HS acts as a diuretic, however in most cases the extract did not significantly influence electrolyte levels. Animal studies have consistently shown that consumption of HS extract reduces blood pressure in a dose dependent manner. In RCTs, the daily consumption of a tea or extract produced from HS calyxes significantly lowered systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults with pre to moderate essential hypertension and type 2 diabetes. In addition, HS tea was as effective at lowering blood pressure as the commonly used blood pressure medication Captropril, but less effective than Lisinopril. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides were lowered in the majority of normolipidemic, hypolipidemic, and diabetic animal models, whereas high-density lipoprotein cholesterol (HDL-C) was generally not affected by the consumption of HS extract. Over half of the RCTs showed that daily consumption of HS tea or extracts had favorable influence on lipid profiles including reduced total cholesterol, LDL-C, triglycerides, as well as increased HDL-C. Anthocyanins found in abundance in HS

  2. Granular biodurable nanomaterials: No convincing evidence for systemic toxicity.

    Science.gov (United States)

    Moreno-Horn, Marcus; Gebel, Thomas

    2014-11-01

    Nanomaterials are usually defined by primary particle diameters ranging from 1 to 100 nm. The scope of this review is an evaluation of experimental animal studies dealing with the systemic levels and putative systemic effects induced by nanoparticles which can be characterized as being granular biodurable particles without known specific toxicity (GBP). Relevant examples of such materials comprise nanosized titanium dioxide (TiO2) and carbon black. The question was raised whether GBP nanomaterials systemically accumulate and may possess a relevant systemic toxicity. With few exceptions, the 56 publications reviewed were not performed using established standard protocols, for example, OECD guidelines but used non-standard study designs. The studies including kinetic investigations indicated that GBP nanomaterials were absorbed and systemically distributed to rather low portions only. There was no valid indication that GPB nanomaterials possess novel toxicological hazard properties. In addition, no convincing evidence for a relevant specific systemic toxicity of GBP nanomaterials could be identified. The minority of the papers reviewed (15/56) investigated both nanosized and microsized GBP materials in parallel. A relevant different translocation of GBP nanomaterials in contrast to GBP micromaterials was not observed in these studies. There was no evidence that GPB nanomaterials possess toxicological properties other than their micromaterial counterparts.

  3. Acute toxicity tests and meta-analysis identify gaps in tropical ecotoxicology for amphibians.

    Science.gov (United States)

    Ghose, Sonia L; Donnelly, Maureen A; Kerby, Jacob; Whitfield, Steven M

    2014-09-01

    Amphibian populations are declining worldwide, particularly in tropical regions where amphibian diversity is highest. Pollutants, including agricultural pesticides, have been identified as a potential contributor to decline, yet toxicological studies of tropical amphibians are very rare. The present study assesses toxic effects on amphibians of 10 commonly used commercial pesticides in tropical agriculture using 2 approaches. First, the authors conducted 8-d toxicity assays with formulations of each pesticide using individually reared red-eyed tree frog (Agalychnis callidryas) tadpoles. Second, they conducted a review of available data for the lethal concentration to kill 50% of test animals from the US Environmental Protection Agency's ECOTOX database to allow comparison with their findings. Lethal concentration estimates from the assays ranged over several orders of magnitude. The nematicides terbufos and ethoprophos and the fungicide chlorothalonil were very highly toxic, with evident effects within an order of magnitude of environmental concentrations. Acute toxicity assays and meta-analysis show that nematicides and fungicides are generally more toxic than herbicides yet receive far less research attention than less toxic herbicides. Given that the tropics have a high diversity of amphibians, the findings emphasize the need for research into the effects of commonly used pesticides in tropical countries and should help guide future ecotoxicological research in tropical regions. © 2014 SETAC.

  4. Multigeneration reproduction and male developmental toxicity studies on atrazine in rats.

    Science.gov (United States)

    DeSesso, John M; Scialli, Anthony R; White, Tacey E K; Breckenridge, Charles B

    2014-06-01

    Reproductive toxicity of Atrazine (ATR) was evaluated in two rat multigenerational studies. Development of male reproductive parameters was evaluated in separate studies after prenatal or postnatal exposure. In multigenerational studies, rats received dietary concentrations of 0, 10, 50, 100 or 500 ppm ATR. In separate studies in female rats, ATR was administered by gavage at 0, 1, 5, 25 or 125 mg/kg/day during pregnancy (GD6-21) or lactation (LD2-21). Plasma testosterone concentration, testicular and epididymal weights, and sperm counts were measured in male offspring on PND70 and 170. In the multigenerational studies, parental systemic toxicity occurred at 500 ppm (38.7 mg/kg/day), but reproductive endpoints were unaffected. In the prenatal study, maternal toxicity and embryo-fetal mortality occurred at 125 mg/kg/day. In male offspring, testosterone levels and sperm counts were unaffected, although the percentage of abnormal sperm increased at 125 mg/kg/day (PND 70) and 25 mg/kg/day (PND170). In the postnatal study, maternal toxicity and reduced body weights of male offspring occurred at 125 mg/kg/day. Additionally, reduced testicular (PND70, PND170) and epididymal (PND70) weights and increased numbers of abnormal sperm (PND70, PND170) were seen, but no changes in plasma testosterone or sperm counts. Dietary administration of ATR did not affect rat reproduction up to a parentally toxic dose of 38.7 mg/kg/day. Some effects on male reproductive system development occurred after high dose, bolus administration to dams, but doses were much higher than expected under normal use conditions. Thus, oral RfDs for ATR would be protective for reproductive effects. © 2014 Wiley Periodicals, Inc.

  5. Larvicidal activity of the water extract of Moringa oleifera seeds against Aedes aegypti and its toxicity upon laboratory animals

    Directory of Open Access Journals (Sweden)

    Paulo M.P. Ferreira

    2009-06-01

    Full Text Available In this work, biological effects of the water extract of Moringa oleifera seeds (WEMOS were assessed on eggs and 3rd instar larvae of Aedes aegypti and on its toxicity upon laboratory animals (Daphnia magna, mice and rats. Crude WEMOS showed a LC50 value of 1260µg/mL, causing 99.2 ± 2.9% larvae mortality within 24 h at 5200µg/mL, though this larvicidal activity has been lost completely at 80ºC/10 min. WEMOS did not demonstrate capacity to prevent egg hatching. After extensive dialyses of the crude WEMOS into watersoluble dialyzable (DF and nondyalizable (NDF fractions, only DF maintained its efficacy to kill larvae. Acute toxicity evaluations on daphnids (EC50 of 188.7µg/mL and mice (LD50 of 446.5 mg/kg body weight pointed out to low toxicity. Despite the thymus hypertrophy, WEMOS revealed to be harmless in orally and subacutelytreated rats. In conclusion, WEMOS has thermostable bioactive compounds against Ae. aegypti larvae with apparent molecular mass lower than 12 kDa and moderately toxic potential.Neste trabalho, o extrato aquoso das sementes de Moringaoleifera (EASMO foi avaliado quanto aos seus efeitos biológicos sobre ovos e larvas de Aedes aegypti no 3ºestágio de desenvolvimento e sua toxicidade sobre animais de laboratório(Daphnia magna, camundongos e ratos. O EASMO bruto revelou uma CL50 de 1.260 µg/mL, causando 99, 2 ± 2, 9% de mortalidade em 24 h na concentração de 5.200 µg/mL, embora o mesmo não tenha sido capaz de impedir a eclosão dos ovos. A atividade larvicida extinguiu-se após aquecimento do extrato a 80ºC/10 min. Diálises sucessivas do EASMO bruto resultaram em duas frações solúveis em água (Fração dializável, FD; Fração nãodializável, FND, dentre as quais apenas a FD mostrou ação larvicida. Testes de toxicidade aguda realizadosem dáfnias (CE50 de 188, 7 µg/mL e camundongos (DL50 de446,5 mg/kg de peso corpóreo evidenciaram baixa toxicidade. Apesar da hipertrofia tímica, o EASMO mostrou ser

  6. Systemic toxicity of dermally applied crude oils in rats

    Energy Technology Data Exchange (ETDEWEB)

    Feuston, M.H.; Mackerer, C.R.; Schreiner, C.A.; Hamilton, C.E. [Stonybrook Labs., Inc., Princeton, NJ (United States)

    1997-12-31

    Two crude oils, differing in viscosity (V) and nitrogen (N) and sulfur (S) content, were evaluated for systemic toxicity, In the Crude I (low V, low N, low S) study, the material was applied to the clipped backs of rats at dose levels of 0, 30, 125, and 500 mg/kg. In the Crude II (high V, high N, moderate S) study, the oil was applied similarly at the same dose levels. The crude oils were applied for 13 wk, 5 d/wk. Exposure sites were not occluded. Mean body weight gain (wk 1-14) was significantly reduced in male rats exposed to Crude II; body weight gain of all other animals was not adversely affected by treatment. An increase in absolute (A) and relative (R) liver weights and a decrease in A and R thymus weights were observed in male and female rats exposed to Crude II at 500 mg/kg; only liver weights (A and R) were adversely affected in male and female rats exposed to Crude I. In general, there was no consistent pattern of toxicity for serum chemistry endpoints; however, more parameters were adversely affected in Crude II-exposed female rats than in the other exposed groups. A consistent pattern of toxicity for hematology endpoints was observed among male rats exposed to Crude I and male and female rats exposed to Crude II. Parameters affected included: Crudes I and II, red blood cell count, hemoglobin, and hematocrit, Crude II, platelet count. Microscopic evaluation of tissues revealed the following treatment-related findings: Crude I, treated skin, thymus, and thyroid; Crude II, bone marrow, treated skin, thymus, and thyroid. The LOEL (lowest observable effect level) for skin irritation and systemic toxicity (based on marginal effects on the thyroid) for both crude oils was 30 mg/kg; effects were more numerous and more pronounced in animals exposed to Crude II. Systemic effects are probably related to concentrations of polycyclic aromatic compounds (PAC) found in crude oil.

  7. Fungal isolates and their toxicity from different ecosystems in ...

    African Journals Online (AJOL)

    ONOS

    2010-08-23

    Aug 23, 2010 ... fungal species behave unexpectedly in different ecosystems. That is why the main ... All the isolates from marine environment were non toxic to brine ... by animals or humans. Severe health problems and death have occurred.

  8. Research perspectives for pre-screening alternatives to animal experimentation

    International Nuclear Information System (INIS)

    Walum, Erik; Hedander, Jan; Garberg, Per

    2005-01-01

    The MEIC study revealed a high predictivity of in vitro cytotoxicity data for human acute systemic toxicity. The idea, put forward by several authors, that compounds that show high cytotoxicity should not need further testing for confirmation but could be assumed toxic also in vivo provides a convenient concept for the selection of the most relevant compounds for further studies in large sets of chemicals, as in the REACH program. The automated techniques applied in high throughput screening (HTS) by the pharmaceutical and biotech industries to select hits in extensive compound collections represent an opportunity to significantly increase the capacity of cytotoxicity testing. Furthermore, it has been suggested that a combination of cytotoxicity data and some basic biokinetic information would greatly improve the accuracy in the extrapolation from in vitro to in vivo and thus make it possible to identify additional toxic compounds that might have escaped in the initial screen. Such information, which can be obtained in a medium throughput screening mode (MTS), includes biotransformation, absorption and some aspects of distribution. The measurement of the net flux of a compound over a cellular barrier, as the one formed in culture by human Caco-2 cells, gives useful, but limited, information on both gut absorption and blood-brain barrier penetration. The test procedures discussed here, as well as other supplementary in vitro tests, cannot always easily be described in terms of animal-based test replacements. In those instances, the necessary test validation cannot be carried out using animal reference data, and prediction models may have to be adapted to new ideas. Consequently, concepts of prospective validation to supplement the now well-established retrospective validation have to be developed

  9. Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

    Science.gov (United States)

    Popov, Dmitri

    found in the umbilical cord and bone marrow as hematopoietic cells, a subset of mesenchymal stem cells, endothelial progenitor cells, endothelial cells of blood vessels, etc. [Beutler et al. 2000 ] Potential mechanisms responsible for radiation-acquired marrow cell failure include direct toxicity , direct damage of hematopoietic multipotential cells or cellular or humoral immune suppression of the marrow multipotential cells. [ Beutler et al. 2000] Methods: These studies were conducted at several different research institutions and laboratories listed as follows: Kazan All-Union Scientific Research Veterinary, Biotechnology Centre of Russian Academy of Science (North Osetia), Institute Belarussian Scientific and Research Institute for Radiobiology in Gomel, the St. Petersburg Veterinary Institute, the Advanced Medical Technology and Systems Inc., Ontario, Canada. The studies were approved by the Animal Care and Use Committee for ethical animal research equivalent, at each institution. A critically important volume of purified Radiation Toxins (RT) was isolated from larger mammalian irradiated animals. Subsequently the RT were characterized chemically and biologically. The experimental design of later studies compared relative toxicity, potential for development of acute radiation hematopoietic syndrome, and potential cloning disorder of multipotential hematopoietic progenitors and their derivative and lethality after intravenous or intramuscular injections of SRD containing Hematopoietic Radiation Toxins. These experiments have employed a wide variety of experimental animals. The animals were irradiated in RUM-17, Puma, and Panorama devices. The dose varied from 0.7Gy to 100Gy. The methods of immune depletion, immuno-lympho plasmasabsorption, as well as direct extraction, were used to refine and purify the specific Radiation Toxins from the central lymph of animals with Hematopoietic forms of Radiation Toxins. Experiments include administration of Hematopoietic

  10. Photocatalytic degradation of rosuvastatin: Analytical studies and toxicity evaluations

    Energy Technology Data Exchange (ETDEWEB)

    Machado, Tiele Caprioli, E-mail: tiele@enq.ufrgs.br [Chemical Engineering Department, Federal University of Rio Grande do Sul, Rua Engenheiro Luiz Englert s/n, CEP: 90040-040 Porto Alegre, RS (Brazil); Pizzolato, Tânia Mara [Chemical Institute, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP: 91501-970 Porto Alegre, RS (Brazil); Arenzon, Alexandre [Ecology Center, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP: 91501-970 Porto Alegre, RS (Brazil); Segalin, Jeferson [Biotechnology Center, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP: 91501-970 Porto Alegre, RS (Brazil); Lansarin, Marla Azário [Chemical Engineering Department, Federal University of Rio Grande do Sul, Rua Engenheiro Luiz Englert s/n, CEP: 90040-040 Porto Alegre, RS (Brazil)

    2015-01-01

    Photocatalytic degradation of rosuvastatin, which is a drug that has been used to reduce blood cholesterol levels, was studied in this work employing ZnO as catalyst. The experiments were carried out in a temperature-controlled batch reactor that was irradiated with UV light. Preliminary the effects of the photocatalyst loading, the initial pH and the initial rosuvastatin concentration were evaluated. The experimental results showed that rosuvastatin degradation is primarily a photocatalytic process, with pseudo-first order kinetics. The byproducts that were generated during the oxidative process were identified using nano-ultra performance liquid chromatography tandem mass spectrometry (nano-UPLC–MS/MS) and acute toxicity tests using Daphnia magna were done to evaluate the toxicity of the untreated rosuvastatin solution and the reactor effluent. - Highlights: • The photocatalytic degradation of rosuvastatin was studied under UV irradiation. • Commercial catalyst ZnO was used. • Initial rosuvastatin concentration, photocatalyst loading and pH were evaluated. • The byproducts generated during the oxidative process were detected and identified. • Acute toxicity tests using Daphnia magna were carried out.

  11. Animal experimentation in Japan: regulatory processes and application for microbiological studies.

    Science.gov (United States)

    Takahashi-Omoe, H; Omoe, K

    2007-07-01

    We have conducted animal experimentation as a highly effective technique in biological studies. Also in microbiological studies, we have used experimentation to prevent and treat many infectious diseases in humans and animals. In Japan, the 'Law for the Humane Treatment and Management of Animals', which covers the consideration of the three R principles, refinement, replacement and reduction for an international humane approach to animal experimentation came into effect in June 2006. Looking towards the straightforward operation of the law in animal experimentation, three government ministries established new basic guidelines for experimentation performed in their jurisdictional research and testing facilities. For future microbiological studies involving animals in Japan, we need to perform animal experiments according to the basic guidelines in association with overseas management systems. In this report, we discussed essential actions for the management of animal experimentation in microbiological studies in Japan.

  12. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    Science.gov (United States)

    2010-07-01

    ... period. Chamber concentration may be measured using gravimetric or analytical methods as appropriate. If...) Conventional acute toxicity test—(1) Principle of the test method. Several groups of experimental animals are... practicable, monitored continuously or intermittently depending on the method of analysis, and recorded at...

  13. Alternative methods for toxicity assessments in fish: comparison of the fish embryo toxicity and the larval growth and survival tests in zebrafish and fathead minnows.

    Science.gov (United States)

    Jeffries, Marlo K Sellin; Stultz, Amy E; Smith, Austin W; Rawlings, Jane M; Belanger, Scott E; Oris, James T

    2014-11-01

    An increased demand for chemical toxicity evaluations has resulted in the need for alternative testing strategies that address animal welfare concerns. The fish embryo toxicity (FET) test developed for zebrafish (Danio rerio) is one such alternative, and the application of the FET test to other species such as the fathead minnow (Pimephales promelas) has been proposed. In the present study, the performances of the FET test and the larval growth and survival (LGS; a standard toxicity testing method) test in zebrafish and fathead minnows were evaluated. This required that testing methods for the fathead minnow FET and zebrafish LGS tests be harmonized with existing test methods and that the performance of these testing strategies be evaluated by comparing the median lethal concentrations of 2 reference toxicants, 3,4-dicholoraniline and ammonia, obtained via each of the test types. The results showed that procedures for the zebrafish FET test can be adapted and applied to the fathead minnow. Differences in test sensitivity were observed for 3,4-dicholoraniline but not ammonia; therefore, conclusions regarding which test types offer the least or most sensitivity could not be made. Overall, these results show that the fathead minnow FET test has potential as an alternative toxicity testing strategy and that further analysis with other toxicants is warranted in an effort to better characterize the sensitivity and feasibility of this testing strategy. © 2014 SETAC.

  14. In vivo animal studies with sugammadex.

    NARCIS (Netherlands)

    Booij, L.H.D.J.; Egmond, J. van; Driessen, J.J.; Boer, H.D. de

    2009-01-01

    A review is presented of animal studies of the selective steroidal neuromuscular blocking drug binding agent sugammadex. These studies demonstrate that sugammadex is faster in onset than the currently used acetylcholinesterase inhibitors, has no muscarinic effects, and is characterised by lack of

  15. Assessing reproductive toxicity of two environmental toxicants with a novel in vitro human spermatogenic model

    Directory of Open Access Journals (Sweden)

    Charles A. Easley, IV

    2015-05-01

    Full Text Available Environmental influences and insults by reproductive toxicant exposure can lead to impaired spermatogenesis or infertility. Understanding how toxicants disrupt spermatogenesis is critical for determining how environmental factors contribute to impaired fertility. While current animal models are available, understanding of the reproductive toxic effects on human fertility requires a more robust model system. We recently demonstrated that human pluripotent stem cells can differentiate into spermatogonial stem cells/spermatogonia, primary and secondary spermatocytes, and haploid spermatids; a model that mimics many aspects of human spermatogenesis. Here, using this model system, we examine the effects of 2-bromopropane (2-BP and 1,2,dibromo-3-chloropropane (DBCP on in vitro human spermatogenesis. 2-BP and DBCP are non-endocrine disrupting toxicants that are known to impact male fertility. We show that acute treatment with either 2-BP or DBCP induces a reduction in germ cell viability through apoptosis. 2-BP and DBCP affect viability of different cell populations as 2-BP primarily reduces spermatocyte viability, whereas DBCP exerts a much greater effect on spermatogonia. Acute treatment with 2-BP or DBCP also reduces the percentage of haploid spermatids. Both 2-BP and DBCP induce reactive oxygen species (ROS formation leading to an oxidized cellular environment. Taken together, these results suggest that acute exposure with 2-BP or DBCP causes human germ cell death in vitro by inducing ROS formation. This system represents a unique platform for assessing human reproductive toxicity potential of various environmental toxicants in a rapid, efficient, and unbiased format.

  16. Acute toxicity assessment of perfluorinated carboxylic acids towards the Baltic microalgae.

    Science.gov (United States)

    Latała, Adam; Nędzi, Marcin; Stepnowski, Piotr

    2009-09-01

    The presence of high-energy carbon-fluorine bonds in perfluoro compounds lends them great stability and causes them to be environmentally persistent. Relatively little is known about the acute toxicity of perfluorinated carboxylic acids (PFCAs) to ecotoxicological markers such as aquatic plants and animals. This study tested the toxicity of these compounds to the green alga Chlorella vulgaris, the diatom Skeletonema marinoi and the blue-green alga Geitlerinema amphibium, which are species representative of the algal flora of the Baltic Sea. The EC(50) values obtained range from 0.28 mM to 12.84 mM. A distinct relationship between hydrophobicity and toxicity is demonstrated. For every extra perfluoromethylene group in the alkyl chain, the toxicity increases twofold. LogEC(50) values are very well correlated linearly with both the number of carbon atoms in the perfluoroalkyl chain and the partition coefficients. The results also indicate that there are clear differences between the responses of particular taxonomic groups of algae: blue-green algae and diatoms are far more sensitive to PFCAs than green algae, probably because of differences in cell wall structure.

  17. Application of Model Animals in the Study of Drug Toxicology

    Science.gov (United States)

    Song, Yagang; Miao, Mingsan

    2018-01-01

    Drug safety is a key factor in drug research and development, Drug toxicology test is the main method to evaluate the safety of drugs, The body condition of an animal has important implications for the results of the study, Previous toxicological studies of drugs were carried out in normal animals in the past, There is a great deviation from the clinical practice.The purpose of this study is to investigate the necessity of model animals as a substitute for normal animals for toxicological studies, It is expected to provide exact guidance for future drug safety evaluation.

  18. Predictive acute toxicity tests with pesticides.

    Science.gov (United States)

    Brown, V K

    1983-01-01

    By definition pesticides are biocidal products and this implies a probability that pesticides may be acutely toxic to species other than the designated target species. The ways in which pesticides are manufactured, formulated, packaged, distributed and used necessitates a potential for the exposure of non-target species although the technology exists to minimize adventitious exposure. The occurrence of deliberate exposure of non-target species due to the misuse of pesticides is known to happen. The array of predictive acute toxicity tests carried out on pesticides and involving the use of laboratory animals can be justified as providing data on which hazard assessment can be based. This paper addresses the justification and rationale of this statement.

  19. Reproductive toxicity parameters and biological monitoring in occupationally and environmentally boron-exposed persons in Bandirma, Turkey.

    Science.gov (United States)

    Duydu, Yalçın; Başaran, Nurşen; Üstündağ, Aylin; Aydin, Sevtap; Ündeğer, Ülkü; Ataman, Osman Yavuz; Aydos, Kaan; Düker, Yalçın; Ickstadt, Katja; Waltrup, Britta Schulze; Golka, Klaus; Bolt, Hermann M

    2011-06-01

    Boric acid and sodium borates have been considered as being "toxic to reproduction and development", following results of animal studies with high doses. Experimentally, a NOAEL (no observed adverse effect level) of 17.5 mg B/kg-bw/day has been identified for the (male) reproductive effects of boron in a multigeneration study of rats, and a NOAEL for the developmental effects in rats was identified at 9.6 mg B/kg-bw/day. These values are being taken as the basis of current EU safety assessments. The present study was conducted to investigate the reproductive effects of boron exposure in workers employed in boric acid production plant in Bandirma, Turkey. In order to characterize the external and internal boron exposures, boron was determined in biological samples (blood, urine, semen), in workplace air, in food, and in water sources. Unfavorable effects of boron exposure on the reproductive toxicity indicators (concentration, motility, morphology of the sperm cells and blood levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone) were not observed. The mean calculated daily boron exposure (DBE) of the highly exposed group was 14.45 ± 6.57 (3.32-35.62) mg/day. These human exposures represent worst-case exposure conditions to boric acid/borates in Turkey. These exposure levels are considerably lower than exposures, which have previously led to reproductive effects in experimental animals. In conclusion, this means that dose levels of boron associated with developmental and reproductive toxic effects in animals are by far not reachable for humans under conditions of normal handling and use.

  20. Rare earth elements in human and animal health: State of art and research priorities

    Energy Technology Data Exchange (ETDEWEB)

    Pagano, Giovanni, E-mail: gbpagano@tin.it [University of Naples “Federico II”, Environmental Hygiene, via Cinthia, I-80126 Naples (Italy); Aliberti, Francesco; Guida, Marco [University of Naples “Federico II”, Environmental Hygiene, via Cinthia, I-80126 Naples (Italy); Oral, Rahime [Ege University, Faculty of Fisheries, TR-35100 Bornova, İzmir (Turkey); Siciliano, Antonietta [University of Naples “Federico II”, Environmental Hygiene, via Cinthia, I-80126 Naples (Italy); Trifuoggi, Marco [University of Naples “Federico II”, Department of Chemical Sciences, I-80126 Naples (Italy); Tommasi, Franca [“Aldo Moro” Bari University, Department of Biology, I-70126 Bari (Italy)

    2015-10-15

    Background: A number of applications have been developed using rare earth elements (REE), implying several human exposures and raising unsolved questions as to REE-associated health effects. Methods: A MedLine survey was retrieved from early reports (1980s) up to June 2015, focused on human and animal exposures to REE. Literature from animal models was selected focusing on REE-associated health effects. Results: Some REE occupational exposures, in jobs such as glass polishers, photoengravers and movie projectionists showed a few case reports on health effects affecting the respiratory system. No case-control or cohort studies of occupational REE exposures were retrieved. Environmental exposures have been biomonitored in populations residing in REE mining areas, showing REE accumulation. The case for a iatrogenic REE exposure was raised by the use of gadolinium-based contrast agents for nuclear magnetic resonance. Animal toxicity studies have shown REE toxicity, affecting a number of endpoints in liver, lungs and blood. On the other hand, the use of REE as feed additives in livestock is referred as a safe and promising device in zootechnical activities, possibly suggesting a hormetic effect both known for REE and for other xenobiotics. Thus, investigations on long-term exposures and observations are warranted. Conclusion: The state of art provides a limited definition of the health effects in occupationally or environmentally REE-exposed human populations. Research priorities should be addressed to case-control or cohort studies of REE-exposed humans and to life-long animal experiments. - Highlights: • An extensive number of activities have been developed utilizing rare earth elements (REE). • The literature of REE-associated health effects in humans, and on animal studies is reviewed. • The main literature gaps are discussed, in epidemiological and in animal studies. • Prospects studies are suggested, aimed at evaluating long-term effects of REE exposures

  1. Rare earth elements in human and animal health: State of art and research priorities

    International Nuclear Information System (INIS)

    Pagano, Giovanni; Aliberti, Francesco; Guida, Marco; Oral, Rahime; Siciliano, Antonietta; Trifuoggi, Marco; Tommasi, Franca

    2015-01-01

    Background: A number of applications have been developed using rare earth elements (REE), implying several human exposures and raising unsolved questions as to REE-associated health effects. Methods: A MedLine survey was retrieved from early reports (1980s) up to June 2015, focused on human and animal exposures to REE. Literature from animal models was selected focusing on REE-associated health effects. Results: Some REE occupational exposures, in jobs such as glass polishers, photoengravers and movie projectionists showed a few case reports on health effects affecting the respiratory system. No case-control or cohort studies of occupational REE exposures were retrieved. Environmental exposures have been biomonitored in populations residing in REE mining areas, showing REE accumulation. The case for a iatrogenic REE exposure was raised by the use of gadolinium-based contrast agents for nuclear magnetic resonance. Animal toxicity studies have shown REE toxicity, affecting a number of endpoints in liver, lungs and blood. On the other hand, the use of REE as feed additives in livestock is referred as a safe and promising device in zootechnical activities, possibly suggesting a hormetic effect both known for REE and for other xenobiotics. Thus, investigations on long-term exposures and observations are warranted. Conclusion: The state of art provides a limited definition of the health effects in occupationally or environmentally REE-exposed human populations. Research priorities should be addressed to case-control or cohort studies of REE-exposed humans and to life-long animal experiments. - Highlights: • An extensive number of activities have been developed utilizing rare earth elements (REE). • The literature of REE-associated health effects in humans, and on animal studies is reviewed. • The main literature gaps are discussed, in epidemiological and in animal studies. • Prospects studies are suggested, aimed at evaluating long-term effects of REE exposures

  2. Toxicity of magnesium alloy biodegradation products in experiment

    Directory of Open Access Journals (Sweden)

    Yu. M. Neryanov

    2013-08-01

    Full Text Available The article presents information on the study of possible toxic effects of biodegradation products of original magnesium-based alloy on laboratory rats. The used laboratory methods of investigation are described. Author has examined biochemical parameters of plasma on the base of which endogenous intoxication in rats was studied. It was found out that products of alloy biological resorption don’t cause toxic effects on tissues and don’t enhance cell destruction, that is evidenced by the absence of signs of endogenous intoxication and oxidative damage of functional macromolecules. Materials and methods. We used white mongrel male rats weighing 220-270 g (n = 20. Fixator consisting of a modified magnesium alloy ML-10 was implanted into the femur muscle mass of the animals of the experimental group (n = 14. The control group consisted of white mongrel male rats weighing 230-250 g (n = 6, which were not subjected to surgery (intact group. The degree of oxidative damage to proteins, the content of the average molecular weight, nucleic acids and the stable metabolites of nitric oxide were evaluated in plasma. Results and discussion. The studies revealed the reliable (relative to the intact group increase in the content of all fractions of middle molecules in the plasma of the experimental group of rats, the increase shows only that the immune system of animals with magnesium implants is in a reactive state and responds with minor release of biologically active substances into the bloodstream. At this rate of endogenous intoxication this exponent usually increases tenfold, but we have not seen that. Levels of stable metabolites of nitric oxide increase insignificantly(1,4 times, that likely indicates more on the start of adaptive signaling processes than a pathological condition. The experimental data concerning the content of nucleic acids in the plasma of animals with magnesium implants testifies in support of this hypothesis. There were no

  3. Reduction of Fumonisin Toxicity by Extrusion and Nixtamalization (Alkaline Cooking).

    Science.gov (United States)

    Voss, Kenneth; Ryu, Dojin; Jackson, Lauren; Riley, Ronald; Gelineau-van Waes, Janee

    2017-08-23

    Fumonisins are mycotoxins found in corn. They are toxic to animals and cause cancer in rodents and neural tube defects in LM/Bc mice. Reducing their concentrations in corn-based foods is therefore desirable. Chemical analysis or in vitro bioassays of food extracts might not detect toxic fumonisin reaction products that are unknown or unextractable from food matrices, thus potentially underestimating in vivo toxicity. The effectiveness of two common cooking methods, extrusion and nixtamalization (alkaline cooking), to reduce the toxicity of fumonisin-contaminated corn grits (extrusion) and whole kernel corn (nixtamalization) was shown by means of rat feeding bioassays using fumonisin-specific kidney effects as indicators of potential toxicity. A third bioassay showed that in contrast to fumonisin B 1 (FB 1 ), hydrolyzed fumonisin B 1 (HFB 1 ; formed from FB 1 during nixtamalization) did not cause neural tube defects in LM/Bc mice. The findings indicate that extrusion and nixtamalization reduce the potential toxicity of FB 1 -contaminated corn.

  4. OECD validation study to assess intra- and inter-laboratory reproducibility of the zebrafish embryo toxicity test for acute aquatic toxicity testing

    NARCIS (Netherlands)

    Busquet, F.; Strecker, R.; Rawlings, J.M.; Belanger, S.E.; Braunbeck, T.; Carr, G.J.; Cenijn, P.H.; Fochtman, P.; Gourmelon, A.; Hübler, N.; Kleensang, A.; Knöbel, M.; Kussatz, C.; Legler, J.; Lillicrap, A.; Martínez-Jerónimo, F.; Polleichtner, C.; Rzodeczko, H.; Salinas, E.; Schneider, K.E.; Scholz, S.; van den Brandhof, E.J.; van der Ven, L.T.; Walter-Rohde, S.; Weigt, S.; Witters, H.; Halder, M.

    2014-01-01

    A The OECD validation study of the zebrafish embryo acute toxicity test (ZFET) for acute aquatic toxicity testing evaluated the ZFET reproducibility by testing 20 chemicals at 5 different concentrations in 3 independent runs in at least 3 laboratories. Stock solutions and test concentrations were

  5. Toxicity of cadmium in Japanese quail: Evaluation of body weight, hepatic and renal function, and cellular immune response

    International Nuclear Information System (INIS)

    Sant'Ana, M.G.; Moraes, R.; Bernardi, M.M.

    2005-01-01

    Cadmium (Cd) is an environmental pollutant that is able to alter the immune function. Previous studies have shown that, in mammals, chronic exposure to Cd decreases the release of macrophagic cytokines such as IL1 and TNα and decreases phagocytosis activity. On the other hand contradictory results showed an increase in the humoral response. The cellular response could be decreased by exposure to Cd. These alterations were observed in mammals. The present study aimed to investigate some of the toxic effects of Cd exposure in birds. In particular, the main objective of this work was to elucidate the effects of exposure to this pollutant on the cellular immune function of the Japanese quail as a model for the study of toxicity in animals exposed in nature. The animals were exposed to the metal (100 ppm, per os) during development, i.e., from 1 to 28 days old. Body weight, biochemical parameters, and cellular immune response were measured during and at the end of treatment. The results showed that the exposure to Cd for 28 days significantly reduced the body weight and induced hepatic toxicity. The kidney function and cellular immune response were not affected by the Cd exposure

  6. The Effect of Digestive Capacity on the Intake Rate of Toxic and Non-Toxic Prey in an Ecological Context.

    Directory of Open Access Journals (Sweden)

    Thomas Oudman

    Full Text Available Digestive capacity often limits food intake rate in animals. Many species can flexibly adjust digestive organ mass, enabling them to increase intake rate in times of increased energy requirement and/or scarcity of high-quality prey. However, some prey species are defended by secondary compounds, thereby forcing a toxin limitation on the forager's intake rate, a constraint that potentially cannot be alleviated by enlarging digestive capacity. Hence, physiological flexibility may have a differential effect on intake of different prey types, and consequently on dietary preferences. We tested this effect in red knots (Calidris canutus canutus, medium-sized migratory shorebirds that feed on hard-shelled, usually mollusc, prey. Because they ingest their prey whole and crush the shell in their gizzard, the intake rate of red knots is generally constrained by digestive capacity. However, one of their main prey, the bivalve Loripes lucinalis, imposes a toxin constraint due to its symbiosis with sulphide-oxidizing bacteria. We manipulated gizzard sizes of red knots through prolonged exposure to hard-shelled or soft foods. We then measured maximum intake rates of toxic Loripes versus a non-toxic bivalve, Dosinia isocardia. We found that intake of Dosinia exponentially increased with gizzard mass, confirming earlier results with non-toxic prey, whereas intake of Loripes was independent of gizzard mass. Using linear programming, we show that this leads to markedly different expected diet preferences in red knots that try to maximize energy intake rate with a small versus a large gizzard. Intra- and inter-individual variation in digestive capacity is found in many animal species. Hence, the here proposed functional link with individual differences in foraging decisions may be general. We emphasize the potential relevance of individual variation in physiology when studying trophic interactions.

  7. Arsenic: it's extent of pollution and toxicosis: An animal perspective

    Directory of Open Access Journals (Sweden)

    Tapan Kumar Das

    2013-02-01

    Full Text Available Arsenic poisoning is now considered as one of the biggest environmental disaster and a major public health issue. Incidence of arsenicpoisoning has been reported from many parts of the world. While Bangladesh and West Bengal (India account for the most of the incidence, occasional reports from Mexico, Taiwan and mainland China have also appeared.It is a natural metalloid found in low concentrations in virtually every part of the environment as it is used in a wide variety of industrial applications, from computers to fireworks. Ground water arsenic is the major source of poisoning in animals and human. About 80% of ingested arsenic is absorbed and metabolized in liver and then excreted through urine and faeces while upon chronic exposure, it is deposited in liver, kidney and skin. Human populations are also being exposed to this poison by consuming the milk of affected animal.Inorganic forms of arsenic are more toxic compared to organic forms. Acute toxicity is rare in nature in comparison to chronic toxicity, which is prevalent in contaminated areas. Most non-ruminants are more susceptible to intoxication than ruminants. Chronic exposure of arsenic in animals and human beings causes severe adverse effects in the form of lowered immunity, diseases and production performances. [Vet World 2013; 6(1.000: 53-58

  8. Modulation of protein fermentation does not affect fecal water toxicity: a randomized cross-over study in healthy subjects.

    Directory of Open Access Journals (Sweden)

    Karen Windey

    Full Text Available Protein fermentation results in production of metabolites such as ammonia, amines and indolic, phenolic and sulfur-containing compounds. In vitro studies suggest that these metabolites might be toxic. However, human and animal studies do not consistently support these findings. We modified protein fermentation in healthy subjects to assess the effects on colonic metabolism and parameters of gut health, and to identify metabolites associated with toxicity.After a 2-week run-in period with normal protein intake (NP, 20 healthy subjects followed an isocaloric high protein (HP and low protein (LP diet for 2 weeks in a cross-over design. Protein fermentation was estimated from urinary p-cresol excretion. Fecal metabolite profiles were analyzed using GC-MS and compared using cluster analysis. DGGE was used to analyze microbiota composition. Fecal water genotoxicity and cytotoxicity were determined using the Comet assay and the WST-1-assay, respectively, and were related to the metabolite profiles.Dietary protein intake was significantly higher during the HP diet compared to the NP and LP diet. Urinary p-cresol excretion correlated positively with protein intake. Fecal water cytotoxicity correlated negatively with protein fermentation, while fecal water genotoxicity was not correlated with protein fermentation. Heptanal, 3-methyl-2-butanone, dimethyl disulfide and 2-propenyl ester of acetic acid are associated with genotoxicity and indole, 1-octanol, heptanal, 2,4-dithiapentane, allyl-isothiocyanate, 1-methyl-4-(1-methylethenyl-benzene, propionic acid, octanoic acid, nonanoic acid and decanoic acid with cytotoxicity.This study does not support a role of protein fermentation in gut toxicity. The identified metabolites can provide new insight into colonic health.ClinicalTrial.gov NCT01280513.

  9. The contribution of studies in animals to the application of hair as an indicator for metals and trace elements in man

    International Nuclear Information System (INIS)

    Kollmer, W.E.

    1994-01-01

    Animal experiments have shown that several parameters, such as sex, age and colour can have an influence on the concentration levels of some elements in hair. The results of these studies have been used to estimate to what extent this is also the case in man. In general, hair can be used for monitoring the environmental exposure when it is not necessary to differentiate between endogenous and exogenous transfer as its is the case of all potentially toxic elements; it can also be used as an indicator for endogenous exposure but in this case the hair should be free from external contamination; hair can be used for identifying the uptake of potentially toxic elements into the body or for estimating their internal levels. For some elements, the content of deep pools are not directly reflected in hair. In the case of essential elements, a major field of potential application is in estimating the adequacy of the dietary supply. In animal nutrition, hair has successfully been used to identify inadequate dietary intake of specific elements; such application is also feasible in man where communities with a different dietary habits can be identified. However, in this case the interactions observed with dietary components and other elements in addition to homeostatic regulations, have to be considered. (author). 156 refs, 3 figs, 1 tab

  10. They see a rat, we seek a cure for diseases: the current status of animal experimentation in medical practice.

    Science.gov (United States)

    Kehinde, Elijah O

    2013-01-01

    The objective of this review article was to examine current and prospective developments in the scientific use of laboratory animals, and to find out whether or not there are still valid scientific benefits of and justification for animal experimentation. The PubMed and Web of Science databases were searched using the following key words: animal models, basic research, pharmaceutical research, toxicity testing, experimental surgery, surgical simulation, ethics, animal welfare, benign, malignant diseases. Important relevant reviews, original articles and references from 1970 to 2012 were reviewed for data on the use of experimental animals in the study of diseases. The use of laboratory animals in scientific research continues to generate intense public debate. Their use can be justified today in the following areas of research: basic scientific research, use of animals as models for human diseases, pharmaceutical research and development, toxicity testing and teaching of new surgical techniques. This is because there are inherent limitations in the use of alternatives such as in vitro studies, human clinical trials or computer simulation. However, there are problems of transferability of results obtained from animal research to humans. Efforts are on-going to find suitable alternatives to animal experimentation like cell and tissue culture and computer simulation. For the foreseeable future, it would appear that to enable scientists to have a more precise understanding of human disease, including its diagnosis, prognosis and therapeutic intervention, there will still be enough grounds to advocate animal experimentation. However, efforts must continue to minimize or eliminate the need for animal testing in scientific research as soon as possible. © 2013 S. Karger AG, Basel.

  11. ALKALOIDAL COMPOSITION AND TOXICITY STUDIES OF THREE ...

    African Journals Online (AJOL)

    Mattock's test for unsaturated pyrrolizidine alkaloids (hepatotoxic) revealed that only C. retusa contained these alkaloids amongst the three species. This indicated that this is a potentially toxic specie. The alkaloids of C. retusa were toxic to albino (Wistar) rats. Marked microscopic lesions were found, principally in the liver.

  12. Strategic focus on 3R principles reveals major reductions in the use of animals in pharmaceutical toxicity testing.

    Directory of Open Access Journals (Sweden)

    Elin Törnqvist

    Full Text Available The principles of the 3Rs, Replacement, Reduction and Refinement, are being increasingly incorporated into legislations, guidelines and practice of animal experiments in order to safeguard animal welfare. In the present study we have studied the systematic application of 3R principles to toxicological research in the pharmaceutical industry, with particular focus on achieving reductions in animal numbers used in regulatory and investigatory in vivo studies. The work also details major factors influencing these reductions including the conception of ideas, cross-departmental working and acceptance into the work process. Data from 36 reduction projects were collected retrospectively from work between 2006 and 2010. Substantial reduction in animal use was achieved by different strategies, including improved study design, method development and project coordination. Major animal savings were shown in both regulatory and investigative safety studies. If a similar (i.e. 53% reduction had been achieved simultaneously within the twelve largest pharmaceutical companies, the equivalent reduction world-wide would be about 150,000 rats annually. The results point at the importance of a strong 3R culture, with scientific engagement, collaboration and a responsive management being vital components. A strong commitment in leadership for the 3R is recommended to be translated into cross-department and inter-profession involvement in projects for innovation, validation and implementation. Synergies between all the three Rs are observed and conclude that in silico-, in vitro- and in vivo-methods all hold the potential for applying the reduction R and should be consequently coordinated at a strategic level.

  13. Characterization of part of the toxic effects due to alpha irradiation and to the physico-chemical properties of some actinides. An in vitro study on the alveolar macrophage

    International Nuclear Information System (INIS)

    Lizon, Celine

    1999-01-01

    The aim of this work was to characterize the specific effects due to radiotoxicity of α irradiation and the chemical toxicity of actinides. This was performed on alveolar macrophages extracted from rats and primates by pulmonary lavage. This was done by an in vitro study using either α irradiation from electrodeposited sources, or soluble actinides and lanthanides added to the culture medium. Necrosis and apoptosis induction were quantified after vital staining. For each treatment, cells were studied 1 or 7 days after plating. After either α irradiation or exposure to elements, the main route of death induced was apoptosis. After α irradiation, alveolar macrophages are very radioresistant cells. The observed D0 was between 30 and 100 Gy, depending on the species studied and the time in culture at exposure. In fact, alveolar macrophages irradiated after 1 week in culture have show less radioresistance than those treated after 1 day. The chemical toxicity of Uranium and Neptunium was independent both of time in culture at exposure and the animal species. The threshold we observed were respectively at 5 10 -4 and 3 10 -6 M. Moreover, within the concentrations studied, Thorium have not shown any toxicity towards alveolar macrophages. 1 day after plating macrophages, lanthanides exerts a higher chemical toxicity than actinides (threshold : 5 10 -6 M, Gadolinium, 5 10 -5 M, Cerium). These toxicities decreases more than 10 times after exposure 7 days after plating or for primates cells. This phenomenon seems to be due to cell harvesting and/or to cell adaptation to culture. Preliminary results show an impairment of cytokines production, which could be specific of the toxic studied. This was observed at concentrations which appeared non toxic as regards to apoptosis induction. The use of primates alveolar macrophages allow us to extrapolate some of the obtained results to Human. (author) [fr

  14. Using quantitative structure-activity relationships (QSAR) to predict toxic endpoints for polycyclic aromatic hydrocarbons (PAH).

    Science.gov (United States)

    Bruce, Erica D; Autenrieth, Robin L; Burghardt, Robert C; Donnelly, K C; McDonald, Thomas J

    2008-01-01

    Quantitative structure-activity relationships (QSAR) offer a reliable, cost-effective alternative to the time, money, and animal lives necessary to determine chemical toxicity by traditional methods. Additionally, humans are exposed to tens of thousands of chemicals in their lifetimes, necessitating the determination of chemical toxicity and screening for those posing the greatest risk to human health. This study developed models to predict toxic endpoints for three bioassays specific to several stages of carcinogenesis. The ethoxyresorufin O-deethylase assay (EROD), the Salmonella/microsome assay, and a gap junction intercellular communication (GJIC) assay were chosen for their ability to measure toxic endpoints specific to activation-, induction-, and promotion-related effects of polycyclic aromatic hydrocarbons (PAH). Shape-electronic, spatial, information content, and topological descriptors proved to be important descriptors in predicting the toxicity of PAH in these bioassays. Bioassay-based toxic equivalency factors (TEF(B)) were developed for several PAH using the quantitative structure-toxicity relationships (QSTR) developed. Predicting toxicity for a specific PAH compound, such as a bioassay-based potential potency (PP(B)) or a TEF(B), is possible by combining the predicted behavior from the QSTR models. These toxicity estimates may then be incorporated into a risk assessment for compounds that lack toxicity data. Accurate toxicity predictions are made by examining each type of endpoint important to the process of carcinogenicity, and a clearer understanding between composition and toxicity can be obtained.

  15. Acute toxicity of subcutaneously administered vitamin E isomers delta- and gamma-tocotrienol in mice.

    Science.gov (United States)

    Swift, Sibyl N; Pessu, Roli L; Chakraborty, Kushal; Villa, Vilmar; Lombardini, Eric; Ghosh, Sanchita P

    2014-01-01

    The toxicity of parenterally administered vitamin E isomers, delta-tocotrienol (DT3) and gamma-tocotrienol (GT3), was evaluated in male and female CD2F1 mice. In an acute toxicity study, a single dose of DT3 or GT3 was administered subcutaneously in a dose range of 200 to 800 mg/kg. A mild to moderately severe dermatitis was observed clinically and microscopically in animals at the injection site at doses above 200 mg/kg. The severity of the reaction was reduced when the drug concentration was lowered. Neither drug produced detectable toxic effects in any other tissue at the doses tested. Based on histopathological analysis for both DT3 and GT3, and macroscopic observations of inflammation at the injection site, a dose of 300 mg/kg was selected as the lowest toxic dose in a 30-day toxicity study performed in male mice. At this dose, a mild skin irritation occurred at the injection site that recovered completely by the end of the experimental period. At a dose of 300 mg/kg of DT3 or GT3, no adverse effects were observed in any tissues or organs. © The Author(s) 2014.

  16. Interaction of engineered nanoparticles with toxic and essential elements

    International Nuclear Information System (INIS)

    Shumakova, A A; Gmoshinski, I V; Khotimchenko, S A; Trushina, E N

    2015-01-01

    Interaction of engineered nanoparticles with toxic and essential trace elements must be taken into consideration when estimating risks of NPs presented in the natural environment. The purpose of this work was to study the possible influence of silica, titanium dioxide (rutile) and fullerenol NPs on the toxicity of cadmium and to research the status of some trace elements and related indices of immune function in experiments on laboratory animals. Young male Wistar rats received cadmium salt (1 mg/kg b.w. Cd) orally for 28 days separately or in conjunction with the said kinds of NPs in different doses. A number of effects was observed as a result of combined action of Cd together with NPs, increase in bioaccumulation of this toxic trace element in the liver was most evident. The observed effects didn't show simple dose- dependence in respect to nanomaterials that should be taken into consideration when assessing the possible risks of joint action of nanoparticles and toxic elements existing in the environment in extremely low doses. Violation of microelement homeostasis caused by the combined action of Cd and NPs can have various adverse effects, such as inhibition of T-cell immunity induced by co-administration of Cd with rutile NPs. (paper)

  17. Interaction of engineered nanoparticles with toxic and essential elements

    Science.gov (United States)

    Shumakova, A. A.; Gmoshinski, I. V.; Khotimchenko, S. A.; Trushina, E. N.

    2015-11-01

    Interaction of engineered nanoparticles with toxic and essential trace elements must be taken into consideration when estimating risks of NPs presented in the natural environment. The purpose of this work was to study the possible influence of silica, titanium dioxide (rutile) and fullerenol NPs on the toxicity of cadmium and to research the status of some trace elements and related indices of immune function in experiments on laboratory animals. Young male Wistar rats received cadmium salt (1 mg/kg b.w. Cd) orally for 28 days separately or in conjunction with the said kinds of NPs in different doses. A number of effects was observed as a result of combined action of Cd together with NPs, increase in bioaccumulation of this toxic trace element in the liver was most evident. The observed effects didn't show simple dose- dependence in respect to nanomaterials that should be taken into consideration when assessing the possible risks of joint action of nanoparticles and toxic elements existing in the environment in extremely low doses. Violation of microelement homeostasis caused by the combined action of Cd and NPs can have various adverse effects, such as inhibition of T-cell immunity induced by co-administration of Cd with rutile NPs.

  18. A high throughput live transparent animal bioassay to identify non-toxic small molecules or genes that regulate vertebrate fat metabolism for obesity drug development

    Directory of Open Access Journals (Sweden)

    Woollett Laura A

    2008-08-01

    Full Text Available Abstract Background The alarming rise in the obesity epidemic and growing concern for the pathologic consequences of the metabolic syndrome warrant great need for development of obesity-related pharmacotherapeutics. The search for such therapeutics is severely limited by the slow throughput of animal models of obesity. Amenable to placement into a 96 well plate, zebrafish larvae have emerged as one of the highest throughput vertebrate model organisms for performing small molecule screens. A method for visually identifying non-toxic molecular effectors of fat metabolism using a live transparent vertebrate was developed. Given that increased levels of nicotinamide adenine dinucleotide (NAD via deletion of CD38 have been shown to prevent high fat diet induced obesity in mice in a SIRT-1 dependent fashion we explored the possibility of directly applying NAD to zebrafish. Methods Zebrafish larvae were incubated with daily refreshing of nile red containing media starting from a developmental stage of equivalent fat content among siblings (3 days post-fertilization, dpf and continuing with daily refreshing until 7 dpf. Results PPAR activators, beta-adrenergic agonists, SIRT-1 activators, and nicotinic acid treatment all caused predicted changes in fat, cholesterol, and gene expression consistent with a high degree of evolutionary conservation of fat metabolism signal transduction extending from man to zebrafish larvae. All changes in fat content were visually quantifiable in a relative fashion using live zebrafish larvae nile red fluorescence microscopy. Resveratrol treatment caused the greatest and most consistent loss of fat content. The resveratrol tetramer Vaticanol B caused loss of fat equivalent in potency to resveratrol alone. Significantly, the direct administration of NAD decreased fat content in zebrafish. Results from knockdown of a zebrafish G-PCR ortholog previously determined to decrease fat content in C. elegans support that future GPR

  19. Reproductive and developmental toxicity of hydrofluorocarbons used as refrigerants.

    Science.gov (United States)

    Ema, Makoto; Naya, Masato; Yoshida, Kikuo; Nagaosa, Ryuichi

    2010-04-01

    The present paper summarizes data on the reproductive and developmental toxicity of hydrofluorocarbons (HFCs), including pentafluoroethane (HFC-125), 1,1,1,2-tetrafluoroethane (HFC-134a), 1,1,1-trifluoroethane (HFC-143a), 1,1-difluoroethane (HFC-152a), difluoromethane (HFC-32) and 1,1,1,3,3-pentafluoropropane (HFC-245fa), used as refrigerants, published in openly available scientific literature. No developmental toxicity of HFC-125 was found even at 50,000 ppm in rats or rabbits. Although HFC-134a exhibited no dominant lethal effect or reproductive toxicity in rats, it caused low body weight in pre- and postnatal offspring and slightly retarded skeletal ossification in fetuses at 50,000 ppm in rats. No maternal or developmental toxicity was noted after exposure to HFC-143a even at 40,000 ppm in rats or rabbits or HFC-152a even at 50,000 ppm in rats. HFC-32 is slightly maternally and developmentally toxic at 50,000 ppm in rats, but not in rabbits. HFC-245fa caused decreases in maternal body weight and food consumption at 10,000 and 50,000 ppm and fetal weight at 50 000ppm. No evidence of teratogenicity for these HFCs was noted in rats or rabbits. There is limited information about the reproductive toxicity of these HFCs. Animal studies remain necessary for risk assessments of chemicals because it is difficult to find alternative methods to determine the toxic effects of chemicals. It is required to reduce emissions of organic vapors containing HFCs to reduce the risk of exposure. Copyright 2009 Elsevier Inc. All rights reserved.

  20. Gut microbiota modulation of chemotherapy efficacy and toxicity.

    Science.gov (United States)

    Alexander, James L; Wilson, Ian D; Teare, Julian; Marchesi, Julian R; Nicholson, Jeremy K; Kinross, James M

    2017-06-01

    Evidence is growing that the gut microbiota modulates the host response to chemotherapeutic drugs, with three main clinical outcomes: facilitation of drug efficacy; abrogation and compromise of anticancer effects; and mediation of toxicity. The implication is that gut microbiota are critical to the development of personalized cancer treatment strategies and, therefore, a greater insight into prokaryotic co-metabolism of chemotherapeutic drugs is now required. This thinking is based on evidence from human, animal and in vitro studies that gut bacteria are intimately linked to the pharmacological effects of chemotherapies (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and novel targeted immunotherapies such as anti-PD-L1 and anti-CLTA-4 therapies. The gut microbiota modulate these agents through key mechanisms, structured as the 'TIMER' mechanistic framework: Translocation, Immunomodulation, Metabolism, Enzymatic degradation, and Reduced diversity and ecological variation. The gut microbiota can now, therefore, be targeted to improve efficacy and reduce the toxicity of current chemotherapy agents. In this Review, we outline the implications of pharmacomicrobiomics in cancer therapeutics and define how the microbiota might be modified in clinical practice to improve efficacy and reduce the toxic burden of these compounds.

  1. Cost-effectiveness analysis of chemical testing for decision-support: How to include animal welfare?

    NARCIS (Netherlands)

    Gabbert, S.G.M.; Ierland, van E.C.

    2010-01-01

    Toxicity testing for regulatory purposes raises the question of test selection for a particular endpoint. Given the public's concern for animal welfare, test selection is a multi-objective decision problem that requires balancing information outcome, animal welfare loss, and monetary testing costs.

  2. Biochemistry of hemlock (Conium maculatum L.) alkaloids and their acute and chronic toxicity in livestock. A review.

    Science.gov (United States)

    López, T A; Cid, M S; Bianchini, M L

    1999-06-01

    The literature on Conium maculatum biochemistry and toxicology, dispersed in a large number of scientific publications, has been put together in this review. C. maculatum is a weed known almost worldwide by its toxicity to many domestic animals and to human beings. It is an Umbelliferae, characterized by long, hollow stems, reaching up to 2 m height at maturity, producing a large amount of lush foliage during its vegetative growth. Its flowers are white, grouped in umbels formed by numerous umbellules. It produces a large number of seeds that allow the plant to form thick stands in modified soils, sometimes encroaching on cultivated fields, to the extent of impeding the growth of any other vegetation inside the C. maculatum area of growth. Eight piperidinic alkaloids have been identified in this species. Two of them, gamma-coniceine and coniine are generally the most abundant and they account for most of the plant acute and chronic toxicity. These alkaloids are synthesized by the plant from eight acetate units from the metabolic pool, forming a polyketoacid which cyclises through an aminotransferase and forms gamma-coniceine as the parent alkaloid via reduction by a NADPH-dependent reductase. The acute toxicity is observed when animals ingest C. maculatum vegetative and flowering plants and seeds. In a short time the alkaloids produce a neuromuscular blockage conducive to death when the respiratory muscles are affected. The chronic toxicity affects only pregnant animals. When they are poisoned by C. maculatum during the fetuses organ formation period, the offspring is born with malformations, mainly palatoschisis and multiple congenital contractures (MCC; frequently described as arthrogryposis). Acute toxicity, if not lethal, may resolve in the spontaneous recovery of the affected animals provided further exposure to C. maculatum is avoided. It has been observed that poisoned animals tend to return to feed on this plant. Chronic toxicity is irreversible and

  3. Comparative metal oxide nanoparticle toxicity using embryonic zebrafish

    Directory of Open Access Journals (Sweden)

    Leah C. Wehmas

    2015-01-01

    Full Text Available Engineered metal oxide nanoparticles (MO NPs are finding increasing utility in the medical field as anticancer agents. Before validation of in vivo anticancer efficacy can occur, a better understanding of whole-animal toxicity is required. We compared the toxicity of seven widely used semiconductor MO NPs made from zinc oxide (ZnO, titanium dioxide, cerium dioxide and tin dioxide prepared in pure water and in synthetic seawater using a five-day embryonic zebrafish assay. We hypothesized that the toxicity of these engineered MO NPs would depend on physicochemical properties. Significant agglomeration of MO NPs in aqueous solutions is common making it challenging to associate NP characteristics such as size and charge with toxicity. However, data from our agglomerated MO NPs suggests that the elemental composition and dissolution potential are major drivers of toxicity. Only ZnO caused significant adverse effects of all MO particles tested, and only when prepared in pure water (point estimate median lethal concentration = 3.5–9.1 mg/L. This toxicity was life stage dependent. The 24 h toxicity increased greatly (∼22.7 fold when zebrafish exposures started at the larval life stage compared to the 24 h toxicity following embryonic exposure. Investigation into whether dissolution could account for ZnO toxicity revealed high levels of zinc ion (40–89% of total sample were generated. Exposure to zinc ion equivalents revealed dissolved Zn2+ may be a major contributor to ZnO toxicity.

  4. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop (presentation)

    Science.gov (United States)

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicit...

  5. Toxicity testing of chemical mixtures: some general aspects and need of international guidelines.

    Science.gov (United States)

    Kappus, H; Yang, R S

    1996-01-01

    The topics discussed by the Working Group on Toxicity Testing of Chemical Mixtures included the following (1) the study designs and results from two real-life exposure scenarios as additional information to the various investigations reported at the conference; (2) the need to take into consideration low-level, long-term exposure (i.e. mimicking human exposure conditions) as well as the issue of limited resources in experimental toxicology studies; (3) the importance of exploring alternative and predictive toxicology methodologies to minimize animal use and to conserve resources; (4) the realization that interactive toxicity should include the consideration of physical and biological agents in addition to chemicals. Two specific studies reported at the conference were also discussed. A number of recommendations were made concerning the planning and implementation of toxicology studies on chemical mixtures.

  6. Some scientific landmarks of the MIT radium toxicity studies

    International Nuclear Information System (INIS)

    Maletskos, C.J.

    1996-01-01

    Until the recent forced termination of the studies on radium toxicity, more than six decades of investigation and research have been devoted to them. These studies involve ∼2400 subjects who were exposed to long-term internally deposited radium [high linear energy transfer (LET)], whose health status was evaluated in great detail and whose radiation dosimetry was based on measurements of their actual radium body burdens. The quality and usefulness of these studies are, therefore, in sharp contrast to other human radiation-exposure studies that involve instantaneous or somewhat protracted external low-LET exposures and inferred radiation dose, as in the atomic-bomb survivor studies. As a consequence of national news in 1932 concerning the gruesome death of a prominent Pittsburgh businessman and sportsman, Robley D. Evans became involved with radium toxicity, and its study became an important project when he joined the faculty of the Massachusetts Institute of Technology physics department and set up the interdisciplinary Radioactivity Center

  7. Immune response is required for the control of in vivo translocation and chronic toxicity of graphene oxide

    Science.gov (United States)

    Wu, Qiuli; Zhao, Yunli; Fang, Jianpeng; Wang, Dayong

    2014-05-01

    Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO toxicity and accumulation in the intestine and maintained the relatively normal immune response of animals. The severe accumulation of OP50 in the intestine might be partially due to the damage by GO on the development and function of AVL and DVB neurons controlling defecation behavior. Reduction of chronic GO toxicity by PEG surface modification largely resulted from the inhibition of OP50 accumulation in the intestine and the maintenance of normal immune response. Our results highlight the key role of innate immunity in regulating in vivo chronic GO toxicity, which will be helpful for our understanding of the interactions between nanomaterials and biological systems during the long-term development of animals.Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO

  8. Intervention of D-glucose ameliorates the toxicity of streptozotocin in accessory sex organs of rat

    International Nuclear Information System (INIS)

    Vikram, A.; Tripathi, D.N.; Ramarao, P.; Jena, G.B.

    2008-01-01

    Streptozotocin (STZ) is a naturally occurring compound isolated from Streptomyces achromogens. It is used extensively for inducing diabetes in experimental animals. Diabetes mellitus is known to have proven adverse effects on male sexual organs and their reproductive functions. The atrophy of prostate gland and other organs of the genitourinary tract were observed in experimental diabetic animals. STZ exhibits a structural resemblance to D-glucose due to the presence of sugar moiety in its structure. Pancreatic β-cells mainly contain GLUT1 and GLUT2 glucose transporters. Possibly due to structural resemblance, STZ and D-glucose, share a common recognition site for entry into the β-cells. The objective of the present study is to evaluate the effect of D-glucose on STZ-induced toxicity in accessory sex organs of male rats. Animals were kept on overnight fasting. One group received vehicle and served as negative control, while all other groups were given STZ (45 mg/kg). Animals that received only STZ served as positive control. The effect of D-glucose was studied on STZ treated animals with different dosage of D-glucose (250, 500, 1000 and 2000 mg/kg). Restoration of body weight, plasma glucose and plasma insulin was evident only at 1000 and 2000 mg/kg of D-glucose. The protective effect of D-glucose is evident only when it is administered simultaneously with STZ. In the present investigation, we report that simultaneous administration of D-glucose along with STZ ameliorates STZ-induced toxicity. This is evident from the restoration of accessory sex organ's weight, cellular morphology as well as insulin level

  9. Developmental toxicity evaluation of inhaled tertiary amyl methyl ether in mice and rats.

    Science.gov (United States)

    Welsch, Frank; Elswick, Barbara; James, R Arden; Marr, Melissa C; Myers, Christina B; Tyl, Rochelle W

    2003-01-01

    This evaluation was part of a much more comprehensive testing program to characterize the mammalian toxicity potential of the gasoline oxygenator additive tertiary amyl methyl ether (TAME), and was initiated upon a regulatory agency mandate. A developmental toxicity hazard identification study was conducted by TAME vapor inhalation exposure in two pregnant rodent species. Timed-pregnant CD(Sprague-Dawley) rats and CD-1 mice, 25 animals per group, inhaled TAME vapors containing 0, 250, 1500 or 3500 ppm for 6 h a day on gestational days 6-16 (mice) or 6-19 (rats). The developmental toxicity hazard potential was evaluated following the study design draft guidelines and end points proposed by the United States Environmental Protection Agency. Based on maternal body weight changes during pregnancy, the no-observable-adverse-effect level (NOAEL) was 250 ppm for maternal toxicity in rats and 1500 ppm for developmental toxicity in rats using the criterion of near-term fetal body weights. In mice, more profound developmental toxicity was present than in rats, at both 1500 and 3500 ppm. At the highest concentration, mouse litters revealed more late fetal deaths, significantly reduced fetal body weights per litter and increased incidences of cleft palate (classified as an external malformation), as well as enlarged lateral ventricles of the cerebrum (a visceral variation). At 1500 ppm, mouse fetuses also exhibited an increased incidence of cleft palate and the dam body weights were reduced. Therefore, the NOAEL for the mouse maternal and developmental toxicity was 250 ppm under the conditions of this study. Copyright 2003 John Wiley & Sons, Ltd.

  10. Genetic and rat toxicity studies of cyclodextrin glucanotransferase

    Directory of Open Access Journals (Sweden)

    Robert R. Maronpot

    Full Text Available Introduction: Microbiologically derived cyclodextrin glucanotransferase (CGTase is used commercially as a processing agent in manufacture of food, pharmaceuticals, and cosmetics. Its toxic potential was evaluated in anticipation of use in the production of alpha-glycosyl isoquercitrin, a water-soluble form of quercetin. Methods: Following OECD guidelines, CGTase, produced by Bacillus pseudalcaliphilus DK-1139, was evaluated in a genotoxicity battery consisting of a bacterial reverse mutation assay, an in vitro micronucleus (MN assay and MN and comet assays using B6C3F1 male and female mice. These same genotoxicity assays were also conducted for sodium sulfate, a contaminant of CGTase preparation. In a 90-day Sprague Dawley rat toxicity study, CGTase was administered by gavage in water at daily doses of 0, 250, 500, and 1000 mg/kg/day. Results: CGTase did not induce mutations with or without metabolic activation in the bacterial reverse mutation assay. Formation of micronuclei was not induced in either in vitro or in vivo MN assays with or without metabolic activation. No induction of DNA damage was detected in male or female mouse liver, stomach, or duodenum in the comet assay. Sodium sulfate also tested negative in these same genotoxicity assays. In the 90-day repeated dose rat study there were no treatment-related adverse clinical or pathological findings. Conclusion: The genotoxicity assays and repeated dose toxicity study support the safe use of CGTase in production of alpha-glycosyl isoquercitrin. Keywords: Micronucleus assay, Comet assay, Enzymatically modified isoquercitrin (EMIQ, Food additive, Flavonol, Sodium sulfate

  11. Acute and chronic toxicity studies of the water extract from dried ...

    African Journals Online (AJOL)

    Acute and chronic toxicities of the water extract from the dried fruits of Terminalia bellerica (Gaertn.) Roxb. were assessed in both female and male rats. For the study of acute toxicity, a single oral administration of the water extract at a dose of 5,000 mg/kg body weight (10 female, 10 male) was performed and the results ...

  12. An integrated multi-label classifier with chemical-chemical interactions for prediction of chemical toxicity effects.

    Science.gov (United States)

    Liu, Tao; Chen, Lei; Pan, Xiaoyong

    2018-05-31

    Chemical toxicity effect is one of the major reasons for declining candidate drugs. Detecting the toxicity effects of all chemicals can accelerate the procedures of drug discovery. However, it is time-consuming and expensive to identify the toxicity effects of a given chemical through traditional experiments. Designing quick, reliable and non-animal-involved computational methods is an alternative way. In this study, a novel integrated multi-label classifier was proposed. First, based on five types of chemical-chemical interactions retrieved from STITCH, each of which is derived from one aspect of chemicals, five individual classifiers were built. Then, several integrated classifiers were built by integrating some or all individual classifiers. By testing the integrated classifiers on a dataset with chemicals and their toxicity effects in Accelrys Toxicity database and non-toxic chemicals with their performance evaluated by jackknife test, an optimal integrated classifier was selected as the proposed classifier, which provided quite high prediction accuracies and wide applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Study of acute biochemical effects of thallium toxicity in mouse urine by NMR spectroscopy.

    Science.gov (United States)

    Tyagi, Ritu; Rana, Poonam; Khan, Ahmad Raza; Bhatnagar, Deepak; Devi, M Memita; Chaturvedi, Shubhra; Tripathi, Rajendra P; Khushu, Subash

    2011-10-01

    Thallium (Tl) is a toxic heavy metal and its exposure to the human body causes physiological and biochemical changes due to its interference with potassium-dependent biological reactions. A high-resolution (1)H NMR spectroscopy based metabonomic approach has been applied for investigating acute biochemical effects caused by thallium sulfate (Tl(2)SO(4)). Male strain A mice were divided in three groups and received three doses of Tl(2)SO(4) (5, 10 and 20 mg kg(-1) b.w., i.p.). Urine samples collected at 3, 24, 72 and 96 h post-dose time points were analyzed by (1)H NMR spectroscopy. NMR spectral data were processed and analyzed using principal components analysis to represent biochemical variations induced by Tl(2)SO(4). Results showed Tl-exposed mice urine to have distinct metabonomic phenotypes and revealed dose- and time-dependent clustering of treated groups. The metabolic signature of urine analysis from Tl(2)SO(4)-treated animals exhibited an increase in the levels of creatinine, taurine, hippurate and β-hydroxybutyrate along with a decrease in energy metabolites trimethylamine and choline. These findings revealed Tl-induced disturbed gut flora, membrane metabolite, energy and protein metabolism, representing physiological dysfunction of vital organs. The present study indicates the great potential of NMR-based metabonomics in mapping metabolic response for toxicology, which could ultimately lead to identification of potential markers for Tl toxicity. Copyright © 2011 John Wiley & Sons, Ltd.

  14. Chemical toxicity approach for emergency response

    International Nuclear Information System (INIS)

    Bauer, T.

    2009-01-01

    In the event of an airborne release of chemical agent or toxic industrial chemical by accidental or intentional means, emergency responders must have a reasonable estimate of the location and size of the resulting hazard area. Emergency responders are responsible for warning persons downwind of the hazard to evacuate or shelter-in-place and must know where to look for casualties after the hazard has passed or dissipated. Given the same source characterization, modern hazard assessment models provide comparable concentration versus location and time estimates. Even urban hazard assessment models often provide similar predictions. There is a major shortcoming, though, in applying model output to estimating human toxicity effects. There exist a variety of toxicity values for non-lethal effects ranging from short-term to occupational to lifetime exposures. For health and safety purposes, these estimates are all safe-sided in converting animal data to human effects and in addressing the most sensitive subset of the population. In addition, these values are usually based on an assumed 1 hour exposure duration at constant concentration and do not reflect either a passing clouds concentration profile or duration. Emergency responders need expected value toxicity parameters rather than the existing safe-sided ones. This presentation will specify the types of toxicity values needed to provide appropriate chemical hazard estimates to emergency responders and will demonstrate how dramatically their use changes the hazard area.(author)

  15. Evaluations of the trans-sulfuration pathway in multiple liver toxicity studies

    International Nuclear Information System (INIS)

    Schnackenberg, Laura K.; Chen Minjun; Sun, Jinchun; Holland, Ricky D.; Dragan, Yvonne; Tong Weida; Welsh, William; Beger, Richard D.

    2009-01-01

    Drug-induced liver injury has been associated with the generation of reactive metabolites, which are primarily detoxified via glutathione conjugation. In this study, it was hypothesized that molecules involved in the synthesis of glutathione would be diminished to replenish the glutathione depleted through conjugation reactions. Since S-adenosylmethionine (SAMe) is the primary source of the sulfur atom in glutathione, UPLC/MS and NMR were used to evaluate metabolites involved with the transulfuration pathway in urine samples collected during studies of eight liver toxic compounds in Sprague-Dawley rats. Urinary levels of creatine were increased on day 1 or day 2 in 8 high dose liver toxicity studies. Taurine concentration in urine was increased in only 3 of 8 liver toxicity studies while SAMe was found to be reduced in 4 of 5 liver toxicity studies. To further validate the results from the metabonomic studies, microarray data from rat liver samples following treatment with acetaminophen was obtained from the Gene Expression Omnibus (GEO) database. Some genes involved in the trans-sulfuration pathway, including guanidinoacetate N-methyltransferase, glycine N-methyltransferase, betaine-homocysteine methyltransferase and cysteine dioxygenase were found to be significantly decreased while methionine adenosyl transferase II, alpha increased at 24 h post-dosing, which is consistent with the SAMe and creatine findings. The metabolic and transcriptomic results show that the trans-sulfuration pathway from SAMe to glutathione was disturbed due to the administration of heptatotoxicants

  16. Isoniazid Toxicity among an Older Veteran Population: A Retrospective Cohort Study.

    Science.gov (United States)

    Vinnard, Christopher; Gopal, Anand; Linkin, Darren R; Maslow, Joel

    2013-01-01

    our objective was to determine the incidence of toxicity among veterans initiating isoniazid therapy for latent tuberculosis infection (LTBI) and determine whether advancing age was a risk factor for toxicity. we performed a retrospective cohort study among all adults initiating isoniazid treatment for LTBI at a Veterans Medical Center from 1999 to 2005. We collected data on patient demographics, co-morbidities, site of initiation, and treatment outcome. 219 patients initiated isoniazid therapy for LTBI during the period of observation, and the completion of therapy was confirmed in 100 patients (46%). Among 18/219 patients (8%) that discontinued therapy due to a documented suspected toxicity, the median time to onset was 3 months (IQR 1-5 months). In an adjusted Cox regression model, there was no association between discontinuation due to suspected toxicity and advancing age (HR 1.03, 95% CI 0.99, 1.07). In contrast, hepatitis C infection was a significant predictor of cessation due to toxicity in the adjusted analysis (HR 3.03, 95% CI 1.08, 8.52). cessation of isoniazid therapy due to suspected toxicity was infrequently observed among a veteran population and was not associated with advancing age. Alternative LTBI treatment approaches should be further examined in the veteran population.

  17. Isoniazid Toxicity among an Older Veteran Population: A Retrospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Christopher Vinnard

    2013-01-01

    Full Text Available Background: our objective was to determine the incidence of toxicity among veterans initiating isoniazid therapy for latent tuberculosis infection (LTBI and determine whether advancing age was a risk factor for toxicity. Methods: we performed a retrospective cohort study among all adults initiating isoniazid treatment for LTBI at a Veterans Medical Center from 1999 to 2005. We collected data on patient demographics, co-morbidities, site of initiation, and treatment outcome. Results: 219 patients initiated isoniazid therapy for LTBI during the period of observation, and the completion of therapy was confirmed in 100 patients (46%. Among 18/219 patients (8% that discontinued therapy due to a documented suspected toxicity, the median time to onset was 3 months (IQR 1–5 months. In an adjusted Cox regression model, there was no association between discontinuation due to suspected toxicity and advancing age (HR 1.03, 95% CI 0.99, 1.07. In contrast, hepatitis C infection was a significant predictor of cessation due to toxicity in the adjusted analysis (HR 3.03, 95% CI 1.08, 8.52. Conclusions: cessation of isoniazid therapy due to suspected toxicity was infrequently observed among a veteran population and was not associated with advancing age. Alternative LTBI treatment approaches should be further examined in the veteran population.

  18. Toxicity of Transition Metal Oxide Nanoparticles: Recent Insights from in vitro Studies

    Directory of Open Access Journals (Sweden)

    Robert S. Aronstam

    2010-10-01

    Full Text Available Nanotechnology has evolved to play a prominent role in our economy. Increased use of nanomaterials poses potential human health risk. It is therefore critical to understand the nature and origin of the toxicity imposed by nanomaterials (nanotoxicity. In this article we review the toxicity of the transition metal oxides in the 4th period that are widely used in industry and biotechnology. Nanoparticle toxicity is compellingly related to oxidative stress and alteration of calcium homeostasis, gene expression, pro-inflammatory responses, and cellular signaling events. The precise physicochemical properties that dictate the toxicity of nanoparticles have yet to be defined, but may include element-specific surface catalytic activity (e.g., metallic, semiconducting properties, nanoparticle uptake, or nanoparticle dissolution. These in vitro studies substantially advance our understanding in mechanisms of toxicity, which may lead to safer design of nanomaterials.

  19. Effects of crude kerosene on testosterone levels, aggression and toxicity in rat

    Directory of Open Access Journals (Sweden)

    Rachel W. Njoroge

    2015-01-01

    Full Text Available The use of crude kerosene as a dietary supplement in boarding schools has been a common practice in east Africa and other countries for many years, with the belief of it reducing the sex drive (libido at the pubertal stage. There is however no scientific basis for this belief. The present study aimed at using a rat animal model to investigate the effects of crude kerosene on serum testosterone levels, aggression and its possible toxic effects. Fifteen male albino rats of approximately similar age and average weights were put into three groups of five animals each; the control group (placebo, low kerosene dose (10 μl/day group and high kerosene dose (300 μl/day group. ELISA was used to determine the serum testosterone levels. During treatment, changes in aggression were observed and noted. Liver toxicity was determined using enzyme assays, total protein and albumin while renal toxicity was monitored using serum creatinine levels. A full hemogram was conducted to determine hematological effects. Various tissue biopsies were obtained and examined using histopathological techniques for evidence of toxicity. Contrary to the common belief, our findings showed an overall increase of serum testosterone levels of up to 66% in the low dose and 75% in the high dose groups, with an increasing trend by the end of the study. The high dose group showed significantly increased levels of white blood cells (WBC (p = 0.036, red blood cells (RBC (p = 0.025, hematocrit (HCT (p = 0.03, red cell distribution width (p = 0.028 and platelets (p = 0.017. The histological results of the stomach indicated chronic gastritis.

  20. Selenium toxicity: cause and effects in aquatic birds

    Science.gov (United States)

    Spallholz, J.E.; Hoffman, D.J.

    2002-01-01

    There are several manners in which selenium may express its toxicity: (1) an important mechanism appears to involve the formation of CH3Se- which either enters a redox cycle and generates superoxide and oxidative stress, or forms free radicals that bind to and inhibit important enzymes and proteins. (2) Excess selenium as selenocysteine results in inhibition of selenium methylation metabolism. As a consequence, concentrations of hydrogen selenide, an intermediate metabolite, accumulate in animals and are hepatotoxic, possibly causing other selenium-related adverse effects. (3) It is also possible that the presence of excess selenium analogs of sulfur-containing enzymes and structural proteins play a role in avian teratogenesis. l-selenomethionine is the most likely major dietary form of selenium encountered by aquatic birds, with lesser amounts of l-selenocysteine ingested from aquatic animal foods. The literature is suggestive that l-selenomethionine is not any more toxic to adult birds than other animals. l-Selenomethionine accumulates in tissue protein of adult birds and in the protein of egg white as would be expected to occur in animals. There is no suggestion from the literature that the levels of l-selenomethionine that would be expected to accumulate in eggs in the absence of environmental concentration of selenium pose harm to the developing embryo. For several species of aquatic birds, levels of Se as selenomethionine in the egg above 3 ppm on a wet weight basis result in reduced hatchability and deformed embryos. The toxicity of l-selenomethionine injected directly into eggs is greater than that found from the entry of l-selenomethionine into the egg from the normal adult diet. This suggests that there is unusual if not abnormal metabolism of l-selenomethionine in the embryo not seen when l-selenomethionine is present in egg white protein where it likely serves as a source of selenium for glutathione peroxidase synthesis in the developing aquatic chick.

  1. Acute toxicity study of methanolic extract of Asparagus pubescens ...

    African Journals Online (AJOL)

    The acute toxicity study of methanolic extract of Asparagus pubescens root was studied on rats. The indices of the study were the liver enzymes (transaminases), cholesterol, creatinine and urea serum levels as well as the ionic analysis. Both alanine aminotransferase (ALT) and. Aspartate aminotransferase (AST) showed a ...

  2. Where are we in the study of animal emotions?

    Science.gov (United States)

    de Vere, Amber J; Kuczaj, Stan A

    2016-09-01

    The study of emotion is rife with debate over issues as fundamental as how to define emotion, and such disputes are particularly common in the nonhuman animal emotion literature. Here, we seek to address some of these issues, especially in terms of how they relate to animal research. Definitional issues are prevalent; clear definitions are often not given of crucial terms, including 'emotion,' and even where provided, such terms may be used inconsistently throughout a single paper. Further disagreement over the structure of emotions, and the nature of conscious experiences involved, leads to consistent differences in authors' criteria for emotions. We concur with those who believe that animals experience emotions and believe that animal emotions should be studied in their own right, not only as they compare to those of humans. We also propose several avenues for future research that we believe will further our understanding of animal emotions. First, the use of multiple measurement methods to assess emotional responses is most likely to provide the information necessary to distinguish between various states and opens the field to more research in harder-to-study species, such as marine mammals. Second, researchers should also endeavor to increase the range of emotions studied, particularly positive ones, in order to move toward a more balanced range of studied states. Finally, we believe that several aspects of personality research would prove beneficial to the study of animal emotions, particularly the distinction between trait and state emotion and the use of the rating method. WIREs Cogn Sci 2016, 7:354-362. doi: 10.1002/wcs.1399 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  3. Alternative (non-animal) methods for cosmetics testing: current status and future prospects-2010.

    Science.gov (United States)

    Adler, Sarah; Basketter, David; Creton, Stuart; Pelkonen, Olavi; van Benthem, Jan; Zuang, Valérie; Andersen, Klaus Ejner; Angers-Loustau, Alexandre; Aptula, Aynur; Bal-Price, Anna; Benfenati, Emilio; Bernauer, Ulrike; Bessems, Jos; Bois, Frederic Y; Boobis, Alan; Brandon, Esther; Bremer, Susanne; Broschard, Thomas; Casati, Silvia; Coecke, Sandra; Corvi, Raffaella; Cronin, Mark; Daston, George; Dekant, Wolfgang; Felter, Susan; Grignard, Elise; Gundert-Remy, Ursula; Heinonen, Tuula; Kimber, Ian; Kleinjans, Jos; Komulainen, Hannu; Kreiling, Reinhard; Kreysa, Joachim; Leite, Sofia Batista; Loizou, George; Maxwell, Gavin; Mazzatorta, Paolo; Munn, Sharon; Pfuhler, Stefan; Phrakonkham, Pascal; Piersma, Aldert; Poth, Albrecht; Prieto, Pilar; Repetto, Guillermo; Rogiers, Vera; Schoeters, Greet; Schwarz, Michael; Serafimova, Rositsa; Tähti, Hanna; Testai, Emanuela; van Delft, Joost; van Loveren, Henk; Vinken, Mathieu; Worth, Andrew; Zaldivar, José-Manuel

    2011-05-01

    The 7th amendment to the EU Cosmetics Directive prohibits to put animal-tested cosmetics on the market in Europe after 2013. In that context, the European Commission invited stakeholder bodies (industry, non-governmental organisations, EU Member States, and the Commission's Scientific Committee on Consumer Safety) to identify scientific experts in five toxicological areas, i.e. toxicokinetics, repeated dose toxicity, carcinogenicity, skin sensitisation, and reproductive toxicity for which the Directive foresees that the 2013 deadline could be further extended in case alternative and validated methods would not be available in time. The selected experts were asked to analyse the status and prospects of alternative methods and to provide a scientifically sound estimate of the time necessary to achieve full replacement of animal testing. In summary, the experts confirmed that it will take at least another 7-9 years for the replacement of the current in vivo animal tests used for the safety assessment of cosmetic ingredients for skin sensitisation. However, the experts were also of the opinion that alternative methods may be able to give hazard information, i.e. to differentiate between sensitisers and non-sensitisers, ahead of 2017. This would, however, not provide the complete picture of what is a safe exposure because the relative potency of a sensitiser would not be known. For toxicokinetics, the timeframe was 5-7 years to develop the models still lacking to predict lung absorption and renal/biliary excretion, and even longer to integrate the methods to fully replace the animal toxicokinetic models. For the systemic toxicological endpoints of repeated dose toxicity, carcinogenicity and reproductive toxicity, the time horizon for full replacement could not be estimated.

  4. Acute Toxicity of Intravenously Administered Titanium Dioxide Nanoparticles in Mice

    OpenAIRE

    Xu, Jiaying; Shi, Hongbo; Ruth, Magaye; Yu, Hongsheng; Lazar, Lissy; Zou, Baobo; Yang, Cui; Wu, Aiguo; Zhao, Jinshun

    2013-01-01

    BACKGROUND: With a wide range of applications, titanium dioxide (TiO₂) nanoparticles (NPs) are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO₂ nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. METHODS: In this study, mice were injected intravenously with a single dose of TiO₂ NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg). Animal mortality, blood biochem...

  5. Protection against methanol-induced retinal toxicity by LED photostimulation

    Science.gov (United States)

    Whelan, Harry T.; Wong-Riley, Margaret T. T.; Eells, Janis T.

    2002-06-01

    We have initiated experiments designed to test the hypothesis that 670-nm Light-Emitting Diode (LED) exposure will attenuate formate-induced retinal dysfunction in a rodent model of methanol toxicity. Methanol intoxication produces toxic injury to the retina. The toxic metabolite formed in methanol intoxication is formic acid, a mitochondrial toxin known to inhibit cytochrome oxidase activity. 670-nm LED light has been hypothesized to act by stimulating cytochrome oxidase activity. To test this hypothesis, one group of animals was intoxicated with methanol, a second group was intoxicated with methanol and LED-treated and a third group was untreated. LED treatment (670 nm for 1 min 45 seconds equals 50 mW/cm2, 4 joules/cm2) was administered at 5, 25, and 50 hours after the initial dose of methanol. At 72 hours of methanol intoxication, retinal function was assessed by measurement of ERG responses and retinas were prepared for histologic analysis. ERG responses recorded in methanol-intoxicated animals revealed profound attenuation of both rod-dominated and UV-cone mediated responses. In contrast, methanol- intoxicated animals exposed to LED treatment exhibited a nearly complete recovery of rod-dominated ERG responses and a slight improvement of UV-cone mediated ERG responses. LED treatment also protected the retina against the histopathologic changes produced by formate in methanol intoxication. These data provide evidence that LED phototherapy protects the retina against the cytotoxic actions of formate and are consistent with the hypothesis that LED photostimulation improves mitochondrial respiratory chain function.

  6. Radioisotopic-excited x-ray fluorescent system for PPM measurement of toxic heavy metals

    International Nuclear Information System (INIS)

    Leddicotte, G.W.; Tolea, F.; Hansen, J.S.

    1974-01-01

    In agricultural research there is a continual awareness of the need to determine the role trace elements have as micronutrients in soil-plant systems. Similarly, these agronomic needs have a strong relationship to the concern other life sciences researchers have about the roles and effects of toxic trace elements on the natural environment and the physiological well-being of man and animals. However, in order for these interest areas to carry out more effective study efforts, more practical and precise analytical methodology and devices need to be developed. This report describes a research effort to develop an analytical system for micronutient as well as toxic elements based on x-ray fluorescence

  7. From Classical Toxicology to Tox21: Some Critical Conceptual and Technological Advances in the Molecular Understanding of the Toxic Response Beginning From the Last Quarter of the 20th Century.

    Science.gov (United States)

    Choudhuri, Supratim; Patton, Geoffrey W; Chanderbhan, Ronald F; Mattia, Antonia; Klaassen, Curtis D

    2018-01-01

    Toxicology has made steady advances over the last 60+ years in understanding the mechanisms of toxicity at an increasingly finer level of cellular organization. Traditionally, toxicological studies have used animal models. However, the general adoption of the principles of 3R (Replace, Reduce, Refine) provided the impetus for the development of in vitro models in toxicity testing. The present commentary is an attempt to briefly discuss the transformation in toxicology that began around 1980. Many genes important in cellular protection and metabolism of toxicants were cloned and characterized in the 80s, and gene expression studies became feasible, too. The development of transgenic and knockout mice provided valuable animal models to investigate the role of specific genes in producing toxic effects of chemicals or protecting the organism from the toxic effects of chemicals. Further developments in toxicology came from the incorporation of the tools of "omics" (genomics, proteomics, metabolomics, interactomics), epigenetics, systems biology, computational biology, and in vitro biology. Collectively, the advances in toxicology made during the last 30-40 years are expected to provide more innovative and efficient approaches to risk assessment. A goal of experimental toxicology going forward is to reduce animal use and yet be able to conduct appropriate risk assessments and make sound regulatory decisions using alternative methods of toxicity testing. In that respect, Tox21 has provided a big picture framework for the future. Currently, regulatory decisions involving drugs, biologics, food additives, and similar compounds still utilize data from animal testing and human clinical trials. In contrast, the prioritization of environmental chemicals for further study can be made using in vitro screening and computational tools. Published by Oxford University Press on behalf of the Society of Toxicology 2017. This work is written by US Government employees and is in the

  8. Why do we study animal toxins?

    Science.gov (United States)

    ZHANG, Yun

    2015-01-01

    Venom (toxins) is an important trait evolved along the evolutionary tree of animals. Our knowledges on venoms, such as their origins and loss, the biological relevance and the coevolutionary patterns with other organisms are greatly helpful in understanding many fundamental biological questions, i.e., the environmental adaptation and survival competition, the evolution shaped development and balance of venoms, and the sophisticated correlations among venom, immunity, body power, intelligence, their genetic basis, inherent association, as well as the cost-benefit and trade-offs of biological economy. Lethal animal envenomation can be found worldwide. However, from foe to friend, toxin studies have led lots of important discoveries and exciting avenues in deciphering and fighting human diseases, including the works awarded the Nobel Prize and lots of key clinic therapeutics. According to our survey, so far, only less than 0.1% of the toxins of the venomous animals in China have been explored. We emphasize on the similarities shared by venom and immune systems, as well as the studies of toxin knowledge-based physiological toxin-like proteins/peptides (TLPs). We propose the natural pairing hypothesis. Evolution links toxins with humans. Our mission is to find out the right natural pairings and interactions of our body elements with toxins, and with endogenous toxin-like molecules. Although, in nature, toxins may endanger human lives, but from a philosophical point of view, knowing them well is an effective way to better understand ourselves. So, this is why we study toxins. PMID:26228472

  9. Oxidation of danofloxacin by free chlorine-kinetic study, structural identification of by-products by LC-MS/MS and potential toxicity of by-products using in silico test.

    Science.gov (United States)

    Yassine, Montaha; Rifai, Ahmad; Doumyati, Samah; Trivella, Aurélien; Mazellier, Patrick; Budzinski, Hélène; Al Iskandarani, Mohamad

    2017-03-01

    In this study, we aimed to investigate the kinetics and the mechanism of reaction of the fluoroquinolone antibacterial danofloxacin (DANO) by free available chlorine (FAC) during water chlorination process. Kinetic study was thus performed at pH 7.2, 20 °C in the presence of an excess of total chlorine. Under these experimental conditions, a second-order reaction rate constant (first-order relative to DANO concentration and first-order relative to FAC concentration) was evaluated to k~1446 M -1  s -1 . Five degradation products were identified at different reaction times. Their structures were investigated by using fragmentations obtained at different CID collision energies in MS/MS experiments. Moreover, the toxicity of the proposed structures was predicted by using T.E.S.T. The results indicated that all by-products may have a developmental toxicity. The oral rat LD 50 concentration was predicted to be lower than that of DANO. Furthermore, two degradation compounds presented a concentration level for fathead minnow LC 50 (96 h) lower than that of DANO and presented toxicity for the marine animals.

  10. The Potential of Adaptive Design in Animal Studies

    Directory of Open Access Journals (Sweden)

    Arshad Majid

    2015-10-01

    Full Text Available Clinical trials are the backbone of medical research, and are often the last step in the development of new therapies for use in patients. Prior to human testing, however, preclinical studies using animal subjects are usually performed in order to provide initial data on the safety and effectiveness of prospective treatments. These studies can be costly and time consuming, and may also raise concerns about the ethical treatment of animals when potentially harmful procedures are involved. Adaptive design is a process by which the methods used in a study may be altered while it is being conducted in response to preliminary data or other new information. Adaptive design has been shown to be useful in reducing the time and costs associated with clinical trials, and may provide similar benefits in preclinical animal studies. The purpose of this review is to summarize various aspects of adaptive design and evaluate its potential for use in preclinical research.

  11. The Potential of Adaptive Design in Animal Studies.

    Science.gov (United States)

    Majid, Arshad; Bae, Ok-Nam; Redgrave, Jessica; Teare, Dawn; Ali, Ali; Zemke, Daniel

    2015-10-12

    Clinical trials are the backbone of medical research, and are often the last step in the development of new therapies for use in patients. Prior to human testing, however, preclinical studies using animal subjects are usually performed in order to provide initial data on the safety and effectiveness of prospective treatments. These studies can be costly and time consuming, and may also raise concerns about the ethical treatment of animals when potentially harmful procedures are involved. Adaptive design is a process by which the methods used in a study may be altered while it is being conducted in response to preliminary data or other new information. Adaptive design has been shown to be useful in reducing the time and costs associated with clinical trials, and may provide similar benefits in preclinical animal studies. The purpose of this review is to summarize various aspects of adaptive design and evaluate its potential for use in preclinical research.

  12. Quantitative structure-activity relationship modeling of the toxicity of organothiophosphate pesticides to Daphnia magna and Cyprinus carpio

    NARCIS (Netherlands)

    Zvinavashe, E.; Du, T.; Griff, T.; Berg, van den J.H.J.; Soffers, A.E.M.F.; Vervoort, J.J.M.; Murk, A.J.; Rietjens, I.

    2009-01-01

    Within the REACH regulatory framework in the EU, quantitative structure-activity relationships (QSAR) models are expected to help reduce the number of animals used for experimental testing. The objective of this study was to develop QSAR models to describe the acute toxicity of organothiophosphate

  13. Dithiocarbamates have a common toxic effect on zebrafish body axis formation

    International Nuclear Information System (INIS)

    Tilton, Fred; La Du, Jane K.; Vue, Meng; Alzarban, Noor; Tanguay, Robert L.

    2006-01-01

    We previously determined that the dithiocarbamate pesticide sodium metam (NaM) and its active ingredient methylisothiocyanate (MITC) were developmentally toxic causing notochord distortions in the zebrafish. In this study, developing zebrafish were exposed to isothiocyanates (ITCs), dithiocarbamates (DTCs) and several degradation products to determine the teratogenic relationship of these chemical classes at the molecular level. All dithiocarbamates tested elicited notochord distortions with notochord NOELs from 2 ), a common DTC degradate, also caused distortions at concentrations >200 times the DTCs. Whole mount in situ hybridization of developmental markers for collagen (collagen2a1), muscle (myoD), and body axis formation (no tail) was perturbed well after cessation of treatment with pyrolidine-DTC (PDTC), dimethyl-DTC (DMDTC), NaM, MITC, and CS 2 . Therefore, distinct albeit related chemical classes share a common toxic effect on zebrafish notochord development. To test the responsiveness of the distortion to metal perturbation, five metal chelators and 2 metals were studied. The membrane permeable copper chelator neocuproine (NCu) was found to cause notochord distortions similar to DTC-related molecules. DMDTC and NCu treated animals were protected with copper, and collagen 2a1 and no tail gene expression patterns were identical to controls in these animals. PDTC, NaM, MITC, and CS 2 were not responsive to copper indicating that the chelation of metals is not the primary means by which these molecules elicit their developmental toxicity. Embryos treated with DMDTC, NaM, and NCu were rescued by adding triciaine (MS-222) which abolishes the spontaneous muscle contractions that begin at 18 hpf. In these animals, only collagen 2a1 expression showed a similar pattern to the other notochord distorting molecules. This indicates that the perturbation of no tail expression is in response to the muscle contractions distorting the notochord, while collagen 2a1 is

  14. Proteomic Signatures of the Zebrafish (Danio rerio) Embryo: Sensitivity and Specificity in Toxicity Assessment of Chemicals.

    Science.gov (United States)

    Hanisch, Karen; Küster, Eberhard; Altenburger, Rolf; Gündel, Ulrike

    2010-01-01

    Studies using embryos of the zebrafish Danio rerio (DarT) instead of adult fish for characterising the (eco-) toxic potential of chemicals have been proposed as animal replacing methods. Effect analysis at the molecular level might enhance sensitivity, specificity, and predictive value of the embryonal studies. The present paper aimed to test the potential of toxicoproteomics with zebrafish eleutheroembryos for sensitive and specific toxicity assessment. 2-DE-based toxicoproteomics was performed applying low-dose (EC(10)) exposure for 48 h with three-model substances Rotenone, 4,6-dinitro-o-cresol (DNOC) and Diclofenac. By multivariate "pattern-only" PCA and univariate statistical analyses, alterations in the embryonal proteome were detectable in nonetheless visibly intact organisms and treatment with the three substances was distinguishable at the molecular level. Toxicoproteomics enabled the enhancement of sensitivity and specificity of the embryonal toxicity assay and bear the potency to identify protein markers serving as general stress markers and early diagnosis of toxic stress.

  15. [Toxicity of the combination of salinomycin and tiamulin in swine].

    Science.gov (United States)

    Wendt, M; Büsing, S; Bollwahn, W

    1997-09-01

    The toxicity of the combination of salinomycin (sal.) and tiamulin (tia.) was investigated in dependence upon dosage and feeding method. In addition the efficacy of a safe dose for prophylactic treatment of dysentery was controlled. Following feed medications were tested for toxic effects in pigs: a) 3 mg sal. + 5 mg tia./kg BW, b) 3 mg sal. + 3 mg tia./kg BW, c) 3 mg sal. + 1 mg tia./kg BW, d) 3 mg sal./kg BW, e) 10 mg tia./kg BW, f) 30 mg tia./kg BW. The daily dose was given for 2 weeks by restricted feeding (twice a day) either as bolus or mixed in the whole ration or by feeding ad libitum. Animals were controlled for clinical symptoms and activities of creatine phosphokinase (CK) and aspartate aminotransferase (ASAT) were evaluated daily. Main clinical signs of poisoning were loss of appetite and locomotor disturbances and could be noticed for dosages of 8, 6 and 4 mg sal. + tia./kg BW. Activities of CK and ASAT were increased dose-related, the feeding method also had an influence on the degree of intoxication. Some animals showed locomotor disturbances without any corresponding changes of CK and ASAT levels. Single pigs remaining without any symptoms even at high dosage pointed to differences in individual susceptibility. Toxicity was not found to be age dependent. Feed medication with 60 ppm sal. + 20 ppm tia. (feeding ad libitum) did not result in any signs of toxicity, however, the transmission of Serpulina hyodysenteriae from infected pigs to healthy, treated control animals could not be inhibited efficiently. Therefore the simultaneous application of salinomycin and tiamulin should be avoided generally, because the risk of intoxication is high and subtherapeutical dosage has an insufficient effectiveness against Serpulina hyodysenteriae.

  16. Anti-colchicine Fab fragments prevent lethal colchicine toxicity in a porcine model: a pharmacokinetic and clinical study.

    Science.gov (United States)

    Eddleston, Michael; Fabresse, Nicolas; Thompson, Adrian; Al Abdulla, Ibrahim; Gregson, Rachael; King, Tim; Astier, Alain; Baud, Frederic J; Clutton, R Eddie; Alvarez, Jean-Claude

    2018-08-01

    Colchicine poisoning is commonly lethal. Colchicine-specific Fab fragments increase rat urinary colchicine clearance and have been associated with a good outcome in one patient. We aimed to develop a porcine model of colchicine toxicity to study the pharmacokinetics and efficacy of ovine Fab. A Göttingen minipig critical care model was established and serial blood samples taken for colchicine and Fab pharmacokinetics, clinical chemistry, and haematology. Animals were euthanised when the mean arterial pressure fell below 45 mmHg without response to vasopressor, or at study completion. Initial studies indicated that oral dosing produced variable pharmacokinetics and time-to-euthanasia. By contrast, intravenous infusion of 0.25 mg/kg colchicine over 1 h produced reproducible pharmacokinetics (AUC 0-20 343 [SD = 21] µg/L/h), acute multi-organ injury, and cardiotoxicity requiring euthanasia a mean of 22.5 (SD = 3.2) h after dosing. A full-neutralising equimolar Fab dose given 6 h after the infusion (50% first hour, 50% next 6 h [to reduce renal-loss of unbound Fab]) produced a 7.35-fold increase in plasma colchicine (AUC 0-20 2,522 [SD = 14] µg/L/h), and removed all free plasma colchicine, but did not prevent toxicity (euthanasia at 29.1 [SD = 3.4] h). Earlier administration over 1 h of the full-neutralising dose, 1 or 3 h after the colchicine, produced a 12.9-fold (AUC 0-20 4,433 [SD = 607] µg/L/h) and 6.0-fold (AUC 0-20 2,047 [SD = 51] µg/L/h) increase in plasma colchicine, respectively, absence of free plasma colchicine until 20 h, and survival to study end without marked cardiotoxicity. Colchicine-specific Fab given early, in equimolar dose, bound colchicine, eliciting its movement into the blood, and preventing severe toxicity. Clinical studies are now needed to determine how soon this antidote must be given to work in human poisoning.

  17. Standardized Total Average Toxicity Score: A Scale- and Grade-Independent Measure of Late Radiotherapy Toxicity to Facilitate Pooling of Data From Different Studies

    Energy Technology Data Exchange (ETDEWEB)

    Barnett, Gillian C., E-mail: gillbarnett@doctors.org.uk [University of Cambridge Department of Oncology, Oncology Centre, Cambridge (United Kingdom); Cancer Research-UK Centre for Genetic Epidemiology and Department of Oncology, Strangeways Research Laboratories, Cambridge (United Kingdom); West, Catharine M.L. [School of Cancer and Enabling Sciences, Manchester Academic Health Science Centre, University of Manchester, Christie Hospital, Manchester (United Kingdom); Coles, Charlotte E. [University of Cambridge Department of Oncology, Oncology Centre, Cambridge (United Kingdom); Pharoah, Paul D.P. [Cancer Research-UK Centre for Genetic Epidemiology and Department of Oncology, Strangeways Research Laboratories, Cambridge (United Kingdom); Talbot, Christopher J. [Department of Genetics, University of Leicester, Leicester (United Kingdom); Elliott, Rebecca M. [School of Cancer and Enabling Sciences, Manchester Academic Health Science Centre, University of Manchester, Christie Hospital, Manchester (United Kingdom); Tanteles, George A. [Department of Clinical Genetics, University Hospitals of Leicester, Leicester (United Kingdom); Symonds, R. Paul [Department of Cancer Studies and Molecular Medicine, University Hospitals of Leicester, Leicester (United Kingdom); Wilkinson, Jennifer S. [University of Cambridge Department of Oncology, Oncology Centre, Cambridge (United Kingdom); Dunning, Alison M. [Cancer Research-UK Centre for Genetic Epidemiology and Department of Oncology, Strangeways Research Laboratories, Cambridge (United Kingdom); Burnet, Neil G. [University of Cambridge Department of Oncology, Oncology Centre, Cambridge (United Kingdom); Bentzen, Soren M. [University of Wisconsin, School of Medicine and Public Health, Department of Human Oncology, Madison, WI (United States)

    2012-03-01

    Purpose: The search for clinical and biologic biomarkers associated with late radiotherapy toxicity is hindered by the use of multiple and different endpoints from a variety of scoring systems, hampering comparisons across studies and pooling of data. We propose a novel metric, the Standardized Total Average Toxicity (STAT) score, to try to overcome these difficulties. Methods and Materials: STAT scores were derived for 1010 patients from the Cambridge breast intensity-modulated radiotherapy trial and 493 women from University Hospitals of Leicester. The sensitivity of the STAT score to detect differences between patient groups, stratified by factors known to influence late toxicity, was compared with that of individual endpoints. Analysis of residuals was used to quantify the effect of these covariates. Results: In the Cambridge cohort, STAT scores detected differences (p < 0.00005) between patients attributable to breast volume, surgical specimen weight, dosimetry, acute toxicity, radiation boost to tumor bed, postoperative infection, and smoking (p < 0.0002), with no loss of sensitivity over individual toxicity endpoints. Diabetes (p = 0.017), poor postoperative surgical cosmesis (p = 0.0036), use of chemotherapy (p = 0.0054), and increasing age (p = 0.041) were also associated with increased STAT score. When the Cambridge and Leicester datasets were combined, STAT was associated with smoking status (p < 0.00005), diabetes (p = 0.041), chemotherapy (p = 0.0008), and radiotherapy boost (p = 0.0001). STAT was independent of the toxicity scale used and was able to deal with missing data. There were correlations between residuals of the STAT score obtained using different toxicity scales (r > 0.86, p < 0.00005 for both datasets). Conclusions: The STAT score may be used to facilitate the analysis of overall late radiation toxicity, from multiple trials or centers, in studies of possible genetic and nongenetic determinants of radiotherapy toxicity.

  18. Toxicity of formaldehyde and acrolein mixtures : in vitro studies using nasal epithelial cells

    NARCIS (Netherlands)

    Cassee, F.R.; Stenhuis, W.S.; Groten, J.P.; Feron, V.J.

    1996-01-01

    In vitro studies with human and rat nasal epithelial cells were carried out to investigate the combined toxicity of formaldehyde and acrolein and the role of aldehyde dehydrogenases in this process. These studies showed that the toxic effect of mixtures of aldehydes was additive. In addition,

  19. Motor vehicle-related air toxics study. Final report

    International Nuclear Information System (INIS)

    1993-04-01

    Section 202 (1)(1) of the Clean Air Act (CAA), as amended (Section 206 of the Clean Air Act Amendments) (CAAA) of 1990 added paragraph (1) to Section 202 of the (CAA), directs the Environmental Protection Agency (EPA) to complete a study by May 15, 1992 of the need for, and feasibility of, controlling emissions of toxic air pollutants which are unregulated under the Act and associated with motor vehicles and motor vehicle fuels. The report has been prepared in response to Section 202 (1)(1). Specific pollutants or pollutant categories which are discussed in the report include benezene, formaldehyde, 1,3-butadiene, acetaldehyde, diesel particulate matter, gasoline particulate matter, and gasoline vapors as well as certain of the metals and motor vehicle-related pollutants identified in Section 112 of the Clean Air Act. The focus of the report is on carcinogenic risk. The study attempts to summarize what is known about motor vehicle-related air toxics and to present all significant scientific opinion on each issue

  20. QSAR Models for Reproductive Toxicity and Endocrine Disruption Activity

    Directory of Open Access Journals (Sweden)

    Marjan Vračko

    2010-03-01

    Full Text Available Reproductive toxicity is an important regulatory endpoint, which is required in registration procedures of chemicals used for different purposes (for example pesticides. The in vivo tests are expensive, time consuming and require large numbers of animals, which must be sacrificed. Therefore an effort is ongoing to develop alternative In vitro and in silico methods to evaluate reproductive toxicity. In this review we describe some modeling approaches. In the first example we describe the CAESAR model for prediction of reproductive toxicity; the second example shows a classification model for endocrine disruption potential based on counter propagation artificial neural networks; the third example shows a modeling of relative binding affinity to rat estrogen receptor, and the fourth one shows a receptor dependent modeling experiment.

  1. The protective effect of pomegranate extract against cisplatin toxicity in rat liver and kidney tissue.

    Science.gov (United States)

    Bakır, Salih; Yazgan, Ümit Can; İbiloğlu, İbrahim; Elbey, Bilal; Kızıl, Murat; Kelle, Mustafa

    2015-01-01

    The purpose of this study was to perform a histopathological investigation, at the light microscopy level, of the protective effects of pomegranate extract in cisplatin-induced liver and kidney damage in rats. Twenty-eight adult male Wistar albino rats were randomly divided into four groups of seven animals: Group 1: Control; Group 2: Treated for 10 consecutive days by gavage with pomegranate juice (2 ml/kg/day); Group 3: Injected intraperitoneally with cisplatin (8 mg/kg body weight, single dose) onset of the day 5, and Group 4: Treated by gavage with pomegranate juice 10 days before and after a single injection of cisplatin onset of the day 5. After 10 days, the animals were sacrificed and their kidneys and liver tissue samples were removed from each animal after experimental procedures. Cisplatin-induced renal and hepatic toxicity and the effect of pomegranate juice were evaluated by histopatological examinations. In the kidney tissue, pomegranate juice significantly ameliorated cisplatin-induced structural alterations when compared with the cisplatin alone group. But in the liver tissue, although pomegranate juice attenuated the cisplatin-induced toxicity only in two rats, significant improvement was not observed. In conclusion, these results demonstrate that the anti-oxidant pomegranate juice might have a protective effect against cisplatin-induced toxicity in rat kidney, but not in liver. Pomegranate juice could be beneficial as a dietary supplement in patients receiving chemotherapy medications.

  2. Avisalmvac: evaluation studies of stability and toxicity

    Directory of Open Access Journals (Sweden)

    Daniela Botus,

    2008-12-01

    Full Text Available In Pasteur Institute laboratories there was developed AVISALMVAC, a vaccine against avian Salmonella, a biological product that contains S. enteritidis and S. typhimurium bacterin, with oil adjuvant. This paper presents the results of the studies regarding the stability and toxicity evaluation of this vaccine stored under conditions recommended by the manufacturer (2-80C at the end of the period of validity. The vaccine stability was assessed by serological and histopathological analysis of samples from SPF chickens vaccinated with the product at the end of the period of validity. The study of Avisalmvac toxicity was carried out by inoculation of the product or its components on Vero cell monolayer, and the effects were microscopically recorded or by MTT test, applied at 6 days post-inoculation. Antibody titers recorded at 2 and 3 weeks post vaccination demonstrated the vaccine ability (used after an year since manufacture to induce synthesis of specific antibodies and therefore, the product stability was proven. Histopathological examinations carried out on samples taken at 18 days post vaccinationfrom the vaccination site (skeletal muscle and skin and spleen, did not show any lesions associated to vaccination with Avisalmvac. The cytotoxicity analysis made by inoculating the vaccine or its components on Vero cell monolayer and the microscopic examination did not record visible cytopathic effects for any vaccine dilutions or vaccine components. The cell metabolism evaluation by MTT assay made at 6 days after vaccine/vaccine components inoculation on Vero monolayer, shown the ability of the vaccine and oil adjuvant to stimulate cell metabolism, and a certain degree of toxicity / inhibition of dehydrogenase metabolism associated to one of emulsifier but at dilutions higher than those used in the vaccine formula.

  3. Evaluating the toxicity of selected types of nanochemicals.

    Science.gov (United States)

    Kumar, Vineet; Kumari, Avnesh; Guleria, Praveen; Yadav, Sudesh Kumar

    2012-01-01

    Nanotechnology is a fast growing field that provides for the development of materials that have new dimensions, novel properties, and a broader array of applications. Various scientific groups are keen about this technology and are devoting themselves to the development of more, new, and better nanomaterials. In the near future, expectations are that no field will be left untouched by the magical benefits available through application of nanotechnology. Presently, there is only limited knowledge concerning the toxicological effects of NPs. However, it is now known that the toxic behavior of NPs differ from their bulk counterparts. Even NPs that have the same chemical composition differ in their toxicological properties; the differences in toxicity depend upon size, shape, and surface covering. Hence, before NPs are commercially used it is most important that they be subjected to appropriate toxicity evaluation. Among the parameters of NPs that must be evaluated for their effect on toxicity are surface charges, types of coating material, and reactivity of NPs. In this article, we have reviewed the literature pertinent to the toxicity of metal oxide NPs, metallic NPs, quantum dots (QDs), silica (SiO2) NPs, carbon nanotubes (CNTs), and certain other carbon nanomaterials (NMs). These NPs have already found a wide range of applications around the world. In vitro and in vivo studies on NPs have revealed that most are toxic to animals. However, their toxic behavior varies with their size, shape, surface charge, type of coating material and reactivity. Dose, route of administration, and exposure are critical factors that affect the degree of toxicity produced by any particular type of NP. It is for this reason that we believe a careful and rigorous toxicity testing is necessary before any NP is declared to be safe for broad use. We also believe that an agreed upon testing system is needed that can be used to suitably, accurately, and economically assess the toxicity of NPs

  4. Toxicity assessment of pesticide triclosan by aquatic organisms and degradation studies.

    Science.gov (United States)

    Taştan, Burcu Ertit; Tekinay, Turgay; Çelik, Hatice Sena; Özdemir, Caner; Cakir, Dilara Nur

    2017-12-01

    Triclosan is considered as an important contaminant and is widely used in personal care products as an antimicrobial agent. This study demonstrates the biodegradation of triclosan by two freshwater microalgae and the acute toxicity of triclosan and 2,4-dichlorophenol. The effects of culture media and light on biodegradation of triclosan and the changing morphology of microalgae were systematically studied. Geitlerinema sp. and Chlorella sp. degraded 82.10% and 92.83% of 3.99 mg/L of triclosan at 10 days, respectively. The microalgal growth inhibition assay confirmed absence of toxic effects of triclosan on Chlorella sp., even at higher concentration (50 mg/L) after 72 h exposure. HPLC analysis showed that 2,4-dichlorophenol was produced as degradation product of triclosan by Geitlerinema sp. and Chlorella sp. This study proved to be beneficial to understand biodegradation and acute toxicity of triclosan by microalgae in order to provide aquatic environmental protection. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Farm workers’ perception of animal welfare – A Danish Study

    DEFF Research Database (Denmark)

    Anneberg, Inger

    2017-01-01

    The welfare of farm animals depends on development in production systems, economic drivers and regulation but also human factors – such as farmers’ perceptions of animal welfare, management strategies, communication, knowledge and training. In this study I have examined the perception of animal...

  6. Emerging Fusarium and Alternaria Mycotoxins: Occurrence, Toxicity and Toxicokinetics

    Directory of Open Access Journals (Sweden)

    Sophie Fraeyman

    2017-07-01

    Full Text Available Emerging Fusarium and Alternaria mycotoxins gain more and more interest due to their frequent contamination of food and feed, although in vivo toxicity and toxicokinetic data are limited. Whereas the Fusarium mycotoxins beauvericin, moniliformin and enniatins particularly contaminate grain and grain-based products, Alternaria mycotoxins are also detected in fruits, vegetables and wines. Although contamination levels are usually low (µg/kg range, higher contamination levels of enniatins and tenuazonic acid may occasionally occur. In vitro studies suggest genotoxic effects of enniatins A, A1 and B1, beauvericin, moniliformin, alternariol, alternariol monomethyl ether, altertoxins and stemphyltoxin-III. Furthermore, in vitro studies suggest immunomodulating effects of most emerging toxins and a reproductive health hazard of alternariol, beauvericin and enniatin B. More in vivo toxicity data on the individual and combined effects of these contaminants on reproductive and immune system in both humans and animals is needed to update the risk evaluation by the European Food Safety Authority. Taking into account new occurrence data for tenuazonic acid, the complete oral bioavailability, the low total body clearance in pigs and broiler chickens and the limited toxicity data, a health risk cannot be completely excluded. Besides, some less known Alternaria toxins, especially the genotoxic altertoxins and stemphyltoxin III, should be incorporated in risk evaluation as well.

  7. Toxicology of ozone on the basis of animal and clinical experimental studies; Toxikologie von Ozon auf der Grundlage tier- und klinisch-experimenteller Untersuchungen

    Energy Technology Data Exchange (ETDEWEB)

    Kappus, H. [Humboldt-Universitaet, Berlin (Germany). Virchow-Klinikum

    2000-07-01

    This synopsis focuses on the toxic effects of ozone in humans and animals following inhalation. It is limited to studies that deal exclusively with ozone. These studies are reviewed with respect to action mechanisms underlying ozone-specific toxicity and, where present, dose-effect relationships. Both aspects today are indispensable for any risk assessment. As there have been very many studies on this issue and the number of publications increases every year, the present paper only quotes a few review articles and does not mention original papers unless they are of recent date or offer new information. [German] Diese Uebersicht konzentriert sich auf die toxischen Effekte von Ozon nach Inhalation bei Mensch und Tier. Nur Untersuchungen mit Ozon alleine werden miteinbezogen. Sie werden hauptsaechlich im Zusammenhang mit dem Wirkungsmechanismus der Ozon-bedingten Toxizitaet und, soweit vorhanden, Konzentrations-Wirkungsbeziehungen behandelt. Beide Aspekte sind heute fuer eine Risikoabschaetzung unerlaesslich. Da sehr viele Untersuchungen vorliegen und die Zahl der Veroeffentlichungen jaehrlich ansteigt, sollen hier nur einige neuere Uebersichtsarbeiten zitiert werden und Originalarbeiten nur dann erwaehnt werden, wenn sie neueren Datums sind bzw. zusaetzliche Informationen bringen. (orig.)

  8. Acute toxicity of live and decomposing green alga Ulva ( Enteromorpha) prolifera to abalone Haliotis discus hannai

    Science.gov (United States)

    Wang, Chao; Yu, Rencheng; Zhou, Mingjiang

    2011-05-01

    From 2007 to 2009, large-scale blooms of green algae (the so-called "green tides") occurred every summer in the Yellow Sea, China. In June 2008, huge amounts of floating green algae accumulated along the coast of Qingdao and led to mass mortality of cultured abalone and sea cucumber. However, the mechanism for the mass mortality of cultured animals remains undetermined. This study examined the toxic effects of Ulva ( Enteromorpha) prolifera, the causative species of green tides in the Yellow Sea during the last three years. The acute toxicity of fresh culture medium and decomposing algal effluent of U. prolifera to the cultured abalone Haliotis discus hannai were tested. It was found that both fresh culture medium and decomposing algal effluent had toxic effects to abalone, and decomposing algal effluent was more toxic than fresh culture medium. The acute toxicity of decomposing algal effluent could be attributed to the ammonia and sulfide presented in the effluent, as well as the hypoxia caused by the decomposition process.

  9. Contaminants in Foods of Animal Origin in Cameroon: A One Health Vision for Risk Management "from Farm to Fork".

    Science.gov (United States)

    Pouokam, Guy B; Foudjo, B U Saha; Samuel, Chi; Yamgai, Philomina Fankam; Silapeux, A Kamda; Sando, Joel Taguemkam; Atonde, G Fankam; Frazzoli, Chiara

    2017-01-01

    Foods of animal origin represent an important share in the diet of Cameroonian populations. Cameroon is known to be a food basket in the west and central Africa sub-region, and an important supplier of foods on the international markets. In the meantime, food importation is continuously increasing to meet the high demand of a more westernized segment of the population. Cereals, fish, sea products, eggs, honey, shrimps, chicken, and feed ingredients are important share in the international trade of agricultural products. Few controls are made on the quality and safety of these products. Certain safety standards do exist but are still yet to be enforced. Inspections done so far by regulatory authorities are partial and do not cover important hazards that require laboratory analysis. The increasing awareness of population, the burden of new types of disease, as well as the recurrence of food scandals have recently launched a scientific and population debate on the contribution of foods items, especially those of animal origin, to the toxic exposure of food producing animals and humans. This paper critically reviews the occurrence of toxicants in most consumed foods of animal origin in Cameroon. This study included the most consumed food of animal origin, identified during the national household budget survey and contributing to 8.1% of the total diet of an individual. Data evaluated suggest an important contamination by toxic metals, mycotoxins, veterinary drugs' residues, and pesticides. The current national legal framework is briefly analyzed to explore possible intervention measures in the frame of the One Health approach.

  10. Differential toxicity and influence of salinity on acute toxicity of ...

    African Journals Online (AJOL)

    Differential toxicity and influence of salinity on acute toxicity of copper sulphate and lead nitrate against Oreochromis niloticus. KA Bawa-Allah, F Osuala, J Effiong. Abstract. This study investigated the salinity-tolerance of Oreochromis niloticus and the influence of salinity changes on the acute toxicities of copper sulphate ...

  11. Occurrence, Toxicity, and Analysis of Major Mycotoxins in Food

    Directory of Open Access Journals (Sweden)

    Ahmad Alshannaq

    2017-06-01

    Full Text Available Mycotoxins are toxic secondary metabolites produced by certain filamentous fungi (molds. These low molecular weight compounds (usually less than 1000 Daltons are naturally occurring and practically unavoidable. They can enter our food chain either directly from plant-based food components contaminated with mycotoxins or by indirect contamination from the growth of toxigenic fungi on food. Mycotoxins can accumulate in maturing corn, cereals, soybeans, sorghum, peanuts, and other food and feed crops in the field and in grain during transportation. Consumption of mycotoxin-contaminated food or feed can cause acute or chronic toxicity in human and animals. In addition to concerns over adverse effects from direct consumption of mycotoxin-contaminated foods and feeds, there is also public health concern over the potential ingestion of animal-derived food products, such as meat, milk, or eggs, containing residues or metabolites of mycotoxins. Members of three fungal genera, Aspergillus, Fusarium, and Penicillium, are the major mycotoxin producers. While over 300 mycotoxins have been identified, six (aflatoxins, trichothecenes, zearalenone, fumonisins, ochratoxins, and patulin are regularly found in food, posing unpredictable and ongoing food safety problems worldwide. This review summarizes the toxicity of the six mycotoxins, foods commonly contaminated by one or more of them, and the current methods for detection and analysis of these mycotoxins.

  12. Dependence of Nanoparticle Toxicity on Their Physical and Chemical Properties

    Science.gov (United States)

    Sukhanova, Alyona; Bozrova, Svetlana; Sokolov, Pavel; Berestovoy, Mikhail; Karaulov, Alexander; Nabiev, Igor

    2018-02-01

    Studies on the methods of nanoparticle (NP) synthesis, analysis of their characteristics, and exploration of new fields of their applications are at the forefront of modern nanotechnology. The possibility of engineering water-soluble NPs has paved the way to their use in various basic and applied biomedical researches. At present, NPs are used in diagnosis for imaging of numerous molecular markers of genetic and autoimmune diseases, malignant tumors, and many other disorders. NPs are also used for targeted delivery of drugs to tissues and organs, with controllable parameters of drug release and accumulation. In addition, there are examples of the use of NPs as active components, e.g., photosensitizers in photodynamic therapy and in hyperthermic tumor destruction through NP incorporation and heating. However, a high toxicity of NPs for living organisms is a strong limiting factor that hinders their use in vivo. Current studies on toxic effects of NPs aimed at identifying the targets and mechanisms of their harmful effects are carried out in cell culture models; studies on the patterns of NP transport, accumulation, degradation, and elimination, in animal models. This review systematizes and summarizes available data on how the mechanisms of NP toxicity for living systems are related to their physical and chemical properties.

  13. [Ethical challenges of genetic manipulation and research with animals].

    Science.gov (United States)

    Rodríguez Yunta, Eduardo

    2012-01-01

    Research with animals presents ethical questions both for being used as models of human diseases and for being a prerequisite for trials in humans, as in the introduction of genetic modifications. Some of these questions refer to the fact that, as models, they do not fully represent the human condition; that conducting toxicity tests causes great harm to animals; that their nature is altered by genetic modifications and that introducing genetically modified organisms is a risk. The use of animals in research for the benefit of humans imposes the moral responsibility to respect them, not making them suffer unnecessarily, since they are living beings capable of feeling.

  14. Using Computational and Mechanical Models to Study Animal Locomotion

    OpenAIRE

    Miller, Laura A.; Goldman, Daniel I.; Hedrick, Tyson L.; Tytell, Eric D.; Wang, Z. Jane; Yen, Jeannette; Alben, Silas

    2012-01-01

    Recent advances in computational methods have made realistic large-scale simulations of animal locomotion possible. This has resulted in numerous mathematical and computational studies of animal movement through fluids and over substrates with the purpose of better understanding organisms’ performance and improving the design of vehicles moving through air and water and on land. This work has also motivated the development of improved numerical methods and modeling techniques for animal locom...

  15. OECD validation study to assess intra- and inter-laboratory reproducibility of the zebrafish embryo toxicity test for acute aquatic toxicity testing.

    Science.gov (United States)

    Busquet, François; Strecker, Ruben; Rawlings, Jane M; Belanger, Scott E; Braunbeck, Thomas; Carr, Gregory J; Cenijn, Peter; Fochtman, Przemyslaw; Gourmelon, Anne; Hübler, Nicole; Kleensang, André; Knöbel, Melanie; Kussatz, Carola; Legler, Juliette; Lillicrap, Adam; Martínez-Jerónimo, Fernando; Polleichtner, Christian; Rzodeczko, Helena; Salinas, Edward; Schneider, Katharina E; Scholz, Stefan; van den Brandhof, Evert-Jan; van der Ven, Leo T M; Walter-Rohde, Susanne; Weigt, Stefan; Witters, Hilda; Halder, Marlies

    2014-08-01

    The OECD validation study of the zebrafish embryo acute toxicity test (ZFET) for acute aquatic toxicity testing evaluated the ZFET reproducibility by testing 20 chemicals at 5 different concentrations in 3 independent runs in at least 3 laboratories. Stock solutions and test concentrations were analytically confirmed for 11 chemicals. Newly fertilised zebrafish eggs (20/concentration and control) were exposed for 96h to chemicals. Four apical endpoints were recorded daily as indicators of acute lethality: coagulation of the embryo, lack of somite formation, non-detachment of the tail bud from the yolk sac and lack of heartbeat. Results (LC50 values for 48/96h exposure) show that the ZFET is a robust method with a good intra- and inter-laboratory reproducibility (CV30%) for some very toxic or volatile chemicals, and chemicals tested close to their limit of solubility. The ZFET is now available as OECD Test Guideline 236. Considering the high predictive capacity of the ZFET demonstrated by Belanger et al. (2013) in their retrospective analysis of acute fish toxicity and fish embryo acute toxicity data, the ZFET is ready to be considered for acute fish toxicity for regulatory purposes. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  16. A flow-cytometric NK-cytotoxicity assay adapted for use in rat repeated dose toxicity studies

    International Nuclear Information System (INIS)

    Marcusson-Staahl, Maritha; Cederbrant, Karin

    2003-01-01

    A recent regulatory document for immunotoxicity testing of new pharmaceutical drugs includes cytotoxic natural killer (NK)-cell function as a required parameter in repeated dose toxicity studies. The classical 51 Cr-release assay is the conventional test for cytotoxicity testing but several drawbacks with this assay has increased the demand for new reliable test systems. Here, we describe the optimisation of a flow-cytometric cytotoxicity assay especially adapted for regulatory rat studies in drug development. The test principle is based on target cell labelling with 5-(6)-carboxy-fluorescein succinimidyl ester (CFSE) and subsequent DNA-labelling with propidium iodide (PI) for identification of target cells with compromised cell membranes. The results are expressed as percentage of dead targets on a cell-to-cell basis. The final format of the assay includes 0.5 ml peripheral blood, 1.25x10 5 effector cells per sample, and collection of 500 target events by flow-cytometry. When NKR-P1+ cells were removed from the effector cell population by magnetic depletion the relative proportion decreased from 6 to 0.08%. The corresponding cytotoxic activity decreased from 68 to 8%. Also, the cytotoxic activity showed a significant and positive correlation with the proportion of NK-cells present in the effector cell suspension. Thus, the cytotoxicity measured is almost exclusively exerted by NK-cells. The current flow-cytometric test benefits from using peripheral blood as a source for effector cells since it will not conflict with the use of spleen for histopathological investigations in repeated dose toxicity studies. Additionally, since only a minimal number of effector cells are required per sample repeated testing of the same animal is enabled

  17. Ethnobotanical Study of Toxic Plants in Ngadiwono Village, Tosari District, Pasuruan Regency, East Java

    Directory of Open Access Journals (Sweden)

    Anggraeni In Oktavia

    2017-08-01

    Full Text Available The society in Ngadiwono village is part of Tengger tribe that depends on their surrounding environment on fulfilling the life necessities. However, the society knowledge obout toxic plant has never been revealed. Therefore, the main objective of this study is to documenting the toxic plants in Ngadiwono village according to society knowledge and scientific study on its toxic content. This study was conducted in Ngadiwono Village, Tosari District, Pasuruan Regency. The informants were chosen by using snowball method (n=14. Interview was conducted using semi-structural method. The collected data was analysed to obtain ICS value (Index Cultural Significance and UVs (Use Value. The identification of toxic compound was based on previous study. The study result identified 8 plants that considered to be toxic by local society: bedor (Girardinia palmata Blume., yellow kecubung (Brugmansia suaveolens Bercht. & J.Presl, white kecubung (Brugmansia suaveolens Bercht. & J.Presl, jarak (Ricinus communis L., yellow terpasan (Cestrum elegans (Brongn. Schltdl, red terpasan (Cestrum elegans (Brongn. Schltdl, kudisan (Euphorbia pulcherrima Willd., and ciplukan (Physalis peruviana L.. The highest ICS value was found in jarak (Ricinus communis. Meanwhile, the lowest ICS value was found in yellow and red terpasan (Cestrum elegans due to its minimum use by local society. The highest UVs was found in kudisan. Keywords: Ethnobotany, Ngadiwono, Plant, Tengger, Toxic

  18. Comparative Ochratoxin Toxicity: A Review of the Available Data

    Directory of Open Access Journals (Sweden)

    Alexandra H. Heussner

    2015-10-01

    Full Text Available Ochratoxins are a group of mycotoxins produced by a variety of moulds. Ochratoxin A (OTA, the most prominent member of this toxin family, was first described by van der Merwe et al. in Nature in 1965. Dietary exposure to OTA represents a serious health issue and has been associated with several human and animal diseases including poultry ochratoxicosis, porcine nephropathy, human endemic nephropathies and urinary tract tumours in humans. More than 30 years ago, OTA was shown to be carcinogenic in rodents and since then extensive research has been performed in order to investigate its mode of action, however, this is still under debate. OTA is regarded as the most toxic family member, however, other ochratoxins or their metabolites and, in particular, ochratoxin mixtures or combinations with other mycotoxins may represent serious threats to human and animal health. This review summarises and evaluates current knowledge about the differential and comparative toxicity of the ochratoxin group.

  19. Protective effect of riboflavin on cisplatin induced toxicities: a gender-dependent study.

    Science.gov (United States)

    Naseem, Imrana; Hassan, Iftekhar; Alhazza, Ibrahim M; Chibber, Sandesh

    2015-01-01

    The toxicity exerted by the anticancer drug, cisplatin in vivo is functional to many factors such as dose, duration, gender and age etc. The present study is aimed to investigate if ameliorative potential of riboflavin on cisplatin induced toxicity is gender dependent. Eighty four adult mice from male and female sex were divided into seven groups (n=6) for both sexes. They were treated with riboflavin (2mg/kg), cisplatin (2mg/kg) and their two different combinations (cisplatin at 2mg/kg with 1mg/kg and 2mg/kg of riboflavin) under photoillumination with their respective controls for the combination groups without photoillumination. After treatment, all groups were sacrificed and their kidney, liver and serum were collected for biochemical estimations, comet assay and histopathology. In the present investigation, it was evident from antioxidant and detoxification studies (SOD, CAT, GSH, GST, MDA and carbonyl level) that the female mice exhibited better tolerance towards cisplatin inducted toxicity and the ameliorative effect of riboflavin against cisplatin toxicity was found stronger in their combination groups as compared to the male groups as the activity of all antioxidant enzymes were found better concomitant with lower level of MDA and carbonyl contents in the female combination groups than their male counterparts. Furthermore, single cell gel electrophoresis and histopathological examination confirmed that restoration of normal nuclear and cellular integrity was more prominent in female with respect to the males after treatment in the combination groups in a dose-dependent manner. Hence, this study reveals that cisplatin is more toxic in male mice and the ameliorative effect of riboflavin against cisplatin toxicity is stronger in female mice. Copyright © 2014. Published by Elsevier GmbH.

  20. Microprocessor-controlled inhalation system for repeated exposure of animals to aerosols

    International Nuclear Information System (INIS)

    Carpenter, R.L.; Barr, F.P.; Leydig, R.L.; Rajala, R.E.

    1979-01-01

    A microprocessor-controlled inhalation exposure system (MCIES) has been built to automate aerosol generation and sampling while controlling exposure time for animal toxicity studies. The system has a time resolution of 0.1 s and automatically sequences the exposure events from initiation to temination of the exposure. The operator is required to preset all airflows, read in a paper tape containing the time sequence of events, and initiate the automatic sequence by closing a switch

  1. Large Dataset of Acute Oral Toxicity Data Created for Testing in Silico Models (ASCCT meeting)

    Science.gov (United States)

    Acute toxicity data is a common requirement for substance registration in the US. Currently only data derived from animal tests are accepted by regulatory agencies, and the standard in vivo tests use lethality as the endpoint. Non-animal alternatives such as in silico models are ...

  2. Human and animal sentinels for shared health risks

    Directory of Open Access Journals (Sweden)

    Peter Rabinowitz, MD, MPH

    2009-03-01

    Full Text Available The tracking of sentinel health events in humans in order to detect and manage disease risks facing a larger population is a well accepted technique applied to influenza, occupational conditions and emerging infectious diseases. Similarly, animal health professionals routinely track disease events in sentinel animal colonies and sentinel herds. The use of animals as sentinels for human health threats, or of humans as sentinels for animal disease risk, dates back at least to the era when coal miners brought caged canaries into mines to provide early warning of toxic gases. Yet the full potential of linking animal and human health information to provide warning of such ‘shared risks’ from environmental hazards has not been realised. Reasons appear to include the professional segregation of human and animal health communities, the separation of human and animal surveillance data and evidence gaps in the linkages between human and animal responses to environmental health hazards. The ‘One Health initiative’ and growing international collaboration in response to pandemic threats, coupled with development in the fields of informatics and genomics, hold promise for improved sentinel event coordination in order to detect and reduce environmental health threats shared between species.

  3. Plasma metabolic profiling analysis of toxicity induced by brodifacoum using metabonomics coupled with multivariate data analysis.

    Science.gov (United States)

    Yan, Hui; Qiao, Zheng; Shen, Baohua; Xiang, Ping; Shen, Min

    2016-10-01

    Brodifacoum is one of the most widely used rodenticides for rodent control and eradication; however, human and animal poisoning due to primary and secondary exposure has been reported since its development. Although numerous studies have described brodifacoum induced toxicity, the precise mechanism still needs to be explored. Gas chromatography mass spectrometry (GC-MS) coupled with an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was applied to characterize the metabolic profile of brodifacoum induced toxicity and discover potential biomarkers in rat plasma. The toxicity of brodifacoum was dose-dependent, and the high-dose group obviously manifested toxicity with subcutaneous hemorrhage. The blood brodifacoum concentration showed a positive relation to the ingestion dose in toxicological analysis. Significant changes of twenty-four metabolites were identified and considered as potential toxicity biomarkers, primarily involving glucose metabolism, lipid metabolism and amino acid metabolism associated with anticoagulant activity, nephrotoxicity and hepatic damage. MS-based metabonomics analysis in plasma samples is helpful to search for potential poisoning biomarkers and to understand the underlying mechanisms of brodifacoum induced toxicity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Reproductive Toxicity of Zishen Yutai Pill in Rats: The Fertility and Early Embryonic Development Study (Segment I

    Directory of Open Access Journals (Sweden)

    Li Zhou

    2016-01-01

    Full Text Available Purpose. This study was aimed to investigate the reproductive toxicity of Zishen Yutai Pill (ZYP on fertility and early embryonic development in rats. Methods. SD rats were randomly divided into 5 groups: vehicle control group (distilled water, i.g., positive control group (80 mg/kg of cyclophosphamide, i.p., and three ZYP-treated groups (3, 6, and 12 g/kg/d, i.e., 12x, 24x, and 48x clinical doses, i.g.. The high dose was set as the maximum gavage dosage. Results. Cyclophosphamide showed diverse hazards, such as decreased weight of male reproductive organs and sperm density (P<0.05. However, there were no obvious effects of ZYP on physical signs, animal behavior, and survival rate, as well as on weight and food intake during the premating and gestation periods. Importantly, there were no significant adverse effects of ZYP on indexes of copulation, fecundity and fertility indexes, weights and coefficients of male reproductive organs, epididymal sperm number and motility, estrous cycle, preimplantation loss rate, and implantation rate. Besides, the numbers of live and resorbed fetuses per litter were not significantly altered. Conclusions. ZYP had no reproductive toxicities on fertility and early embryonic development in rats at 48x equivalent clinical doses.

  5. ProTox: a web server for the in silico prediction of rodent oral toxicity.

    Science.gov (United States)

    Drwal, Malgorzata N; Banerjee, Priyanka; Dunkel, Mathias; Wettig, Martin R; Preissner, Robert

    2014-07-01

    Animal trials are currently the major method for determining the possible toxic effects of drug candidates and cosmetics. In silico prediction methods represent an alternative approach and aim to rationalize the preclinical drug development, thus enabling the reduction of the associated time, costs and animal experiments. Here, we present ProTox, a web server for the prediction of rodent oral toxicity. The prediction method is based on the analysis of the similarity of compounds with known median lethal doses (LD50) and incorporates the identification of toxic fragments, therefore representing a novel approach in toxicity prediction. In addition, the web server includes an indication of possible toxicity targets which is based on an in-house collection of protein-ligand-based pharmacophore models ('toxicophores') for targets associated with adverse drug reactions. The ProTox web server is open to all users and can be accessed without registration at: http://tox.charite.de/tox. The only requirement for the prediction is the two-dimensional structure of the input compounds. All ProTox methods have been evaluated based on a diverse external validation set and displayed strong performance (sensitivity, specificity and precision of 76, 95 and 75%, respectively) and superiority over other toxicity prediction tools, indicating their possible applicability for other compound classes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. A 90-day dietary toxicity study of genetically modified rice T1C-1 expressing Cry1C protein in Sprague Dawley rats.

    Directory of Open Access Journals (Sweden)

    Xueming Tang

    Full Text Available In a 90-day study, Sprague Dawley rats were fed transgenic T1C-1 rice expressing Cry1C protein and were compared with rats fed non-transgenic parental rice Minghui 63 and rats fed a basal diet. No adverse effects on animal behavior or weight gain were observed during the study. Blood samples were collected and analyzed, and standard hematological and biochemical parameters were compared. A few of these parameters were found to be significantly different, but were within the normal reference intervals for rats of this breed and age, and were thus not considered to be treatment-related. Following sacrifice, a large number of organs were weighed, and macroscopic and histopathological examinations were performed with no changes reported. The aim of this study was to use a known animal model to determine the safety of the genetically modified (GM rice T1C-1. The results showed no adverse or toxic effects due to T1C-1 rice when tested in this 90-day study.

  7. A 90-day dietary toxicity study of genetically modified rice T1C-1 expressing Cry1C protein in Sprague Dawley rats.

    Science.gov (United States)

    Tang, Xueming; Han, Fangting; Zhao, Kai; Xu, Yan; Wu, Xiao; Wang, Jinbin; Jiang, Lingxi; Shi, Wei

    2012-01-01

    In a 90-day study, Sprague Dawley rats were fed transgenic T1C-1 rice expressing Cry1C protein and were compared with rats fed non-transgenic parental rice Minghui 63 and rats fed a basal diet. No adverse effects on animal behavior or weight gain were observed during the study. Blood samples were collected and analyzed, and standard hematological and biochemical parameters were compared. A few of these parameters were found to be significantly different, but were within the normal reference intervals for rats of this breed and age, and were thus not considered to be treatment-related. Following sacrifice, a large number of organs were weighed, and macroscopic and histopathological examinations were performed with no changes reported. The aim of this study was to use a known animal model to determine the safety of the genetically modified (GM) rice T1C-1. The results showed no adverse or toxic effects due to T1C-1 rice when tested in this 90-day study.

  8. Labelled radioactive adenosinphosphates for the determination of toxic action

    International Nuclear Information System (INIS)

    Tahbaz, Z.

    1983-01-01

    Normal house-flies had been fed with carrier free radiophosphate (phosphorus). Many phosphorous containing substances in the tissue of the housefly are labelled with radiophosphorus by this procedure. Radiophosphorus is also found in the nucleotides of the housefly after applying radioactive phosphate. Suitable methods for processing and separation had been selected and worked out to isolate 32 P-adenosin-triphosphate 32 P-adenosin-diphosphate, 32 P-adenosin-monophosphate and 32 P-phosphate. Working at low temperature prevents chemical changes of the nucleotides. Extraction and thin layer chromatorgraphy turned out to be effective separation procedures for preparing samples for radioactivity measurement of the nucleotides. Autoradiographic techniques, scanning and liquid scitillation counting had been used for radioactivity measurements of the radioactive zones at the chromatograms. The results of these measurements provide information concerning the normal composition of adenosin-phosphates in the tissues of the housefly. If the animals are exposed to toxic chemicals, to insecticides, the composition of the phosphate containing compounds is changing. The concentration of adenosin-triphosphate is decreasing and the concentration of phosphate is increasing. This can be very easily shown by scanning the chromatograms of the extracts of the muscles of houseflies after feeding the animals with radioactive phosphate. Using this method, it is possible to show the toxic action of insecticides upon the metabolism of adenosin-phosphates. The decrease of the radioactivity at the zone of the adenosin-triphosphate and the increase of the radioactivity at the phosphate zone corresponds to the toxic action of foreign chemicals like insecticides. By using this tracer technique, it may be possible to investigate the toxic action of several toxic chemicals, if they are applied at the same time, thus investigating synergetic actions of environmental poisons. (Author)

  9. Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity

    Directory of Open Access Journals (Sweden)

    Bryan L. Stegelmeier

    2016-11-01

    Full Text Available Dehydropyrrolizidine alkaloid (DHPA-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication is generally caused by contaminated grains, feed, flour, and breads that result in acute, high-dose, short-duration poisoning. Acute poisoning produces hepatic necrosis that is usually confirmed histologically, epidemiologically, and chemically. Less is known about chronic poisoning that may result when plant populations are sporadic, used as tisanes or herbal preparations, or when DHPAs contaminate milk, honey, pollen, or other animal-derived products. Such subclinical exposures may contribute to the development of chronic disease in humans or may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low DHPA doses of short durations. These concerns have moved some governments to prohibit or limit human exposure to DHPAs. The purpose of this review is to summarize some recent DHPA research, including in vitro and in vivo DHPA toxicity and carcinogenicity reports, and the implications of these findings with respect to diagnosis and prognosis for human and animal health.

  10. Developmental toxicity of low generation PAMAM dendrimers in zebrafish

    International Nuclear Information System (INIS)

    King Heiden, Tisha C.; Dengler, Emelyne; Kao, Weiyuan John; Heideman, Warren; Peterson, Richard E.

    2007-01-01

    Biological molecules and intracellular structures operate at the nanoscale; therefore, development of nanomedicines shows great promise for the treatment of disease by using targeted drug delivery and gene therapies. PAMAM dendrimers, which are highly branched polymers with low polydispersity and high functionality, provide an ideal architecture for construction of effective drug carriers, gene transfer devices and imaging of biological systems. For example, dendrimers bioconjugated with selective ligands such as Arg-Gly-Asp (RGD) would theoretically target cells that contain integrin receptors and show potential for use as drug delivery devices. While RGD-conjugated dendrimers are generally considered not to be cytotoxic, there currently exists little information on the risks that such materials pose to human health. In an effort to compliment and extend the knowledge gleaned from cell culture assays, we have used the zebrafish embryo as a rapid, medium throughput, cost-effective whole-animal model to provide a more comprehensive and predictive developmental toxicity screen for nanomaterials such as PAMAM dendrimers. Using the zebrafish embryo, we have assessed the developmental toxicity of low generation (G3.5 and G4) PAMAM dendrimers, as well as RGD-conjugated forms for comparison. Our results demonstrate that G4 dendrimers, which have amino functional groups, are toxic and attenuate growth and development of zebrafish embryos at sublethal concentrations; however, G3.5 dendrimers, with carboxylic acid terminal functional groups, are not toxic to zebrafish embryos. Furthermore, RGD-conjugated G4 dendrimers are less potent in causing embryo toxicity than G4 dendrimers. RGD-conjugated G3.5 dendrimers do not elicit toxicity at the highest concentrations tested and warrant further study for use as a drug delivery device

  11. [Can nitrates lead to indirect toxicity?].

    Science.gov (United States)

    Hamon, M

    2007-09-01

    For many years, nitrates have been used, at low dosages, as an additive in salted food. New laws have been promulgated to limit their concentration in water due to increased levels found in soils, rivers and even the aquifer. Although nitrate ions themselves have not toxic properties, bacterial reduction into nitrite ions (occurring even in aqueous medium) can lead to nitrous anhydride, which in turn generates nitrosonium ions. Nitrosium ions react with secondary amine to give nitrosamines, many of which are cancer-inducing agents at very low doses. Opinions on this toxicity are clear-cut and difficult to reconcile. In fact, increased levels are due, in a large part, to the use of nitrates as fertiliéers but also to bacterial transformation of human and animal nitrogenous wastes such as urea.

  12. Structural studies on a non-toxic homologue of type II RIPs from ...

    Indian Academy of Sciences (India)

    Structural studies on a non-toxic homologue of type II RIPs from bitter gourd: Molecular basis of non-toxicity, conformational selection and glycan structure. MS accepted http://www.ias.ac.in/jbiosci. THYAGESHWAR CHANDRAN, ALOK SHARMA and M VIJAYAN. J. Biosci. 40(5), October 2015, 929–941, © Indian Academy of ...

  13. Assessment of toxicity and biodistribution of recombinant AAV8 vector–mediated immunomodulatory gene therapy in mice with Pompe disease

    Directory of Open Access Journals (Sweden)

    Gensheng Wang

    2014-01-01

    Full Text Available A preclinical safety study was conducted to evaluate the short- and long-term toxicity of a recombinant adeno-associated virus serotype 8 (AAV2/8 vector that has been developed as an immune-modulatory adjunctive therapy to recombinant human acid α-glucosidase (rhGAA, Myozyme enzyme replacement treatment (ERT for patients with Pompe disease (AAV2/8-LSPhGAApA. The AAV2/8-LSPhGAApA vector at 1.6 × 1013 vector particles/kg, after intravenous injection, did not cause significant short- or long-term toxicity. Recruitment of CD4+ (but not CD8+ lymphocytes to the liver was elevated in the vector-dosed male animals at study day (SD 15, and in group 8 animals at SD 113, in comparison to their respective control animals. Administration of the vector, either prior to or after the one ERT injection, uniformly prevented the hypersensitivity induced by subsequent ERT in males, but not always in female animals. The vector genome was sustained in all tissues through 16-week postdosing, except for in blood with a similar tissue tropism between males and females. Administration of the vector alone, or combined with the ERT, was effective in producing significantly increased GAA activity and consequently decreased glycogen accumulation in multiple tissues, and the urine biomarker, Glc4, was significantly reduced. The efficacy of the vector (or with ERT was better in males than in females, as demonstrated both by the number of tissues showing significantly effective responses and the extent of response in a given tissue. Given the lack of toxicity for AAV2/8LSPhGAApA, further consideration of clinical translation is warranted in Pompe disease.

  14. Contaminants in Foods of Animal Origin in Cameroon: A One Health Vision for Risk Management “from Farm to Fork”

    Directory of Open Access Journals (Sweden)

    Guy B. Pouokam

    2017-09-01

    Full Text Available Foods of animal origin represent an important share in the diet of Cameroonian populations. Cameroon is known to be a food basket in the west and central Africa sub-region, and an important supplier of foods on the international markets. In the meantime, food importation is continuously increasing to meet the high demand of a more westernized segment of the population. Cereals, fish, sea products, eggs, honey, shrimps, chicken, and feed ingredients are important share in the international trade of agricultural products. Few controls are made on the quality and safety of these products. Certain safety standards do exist but are still yet to be enforced. Inspections done so far by regulatory authorities are partial and do not cover important hazards that require laboratory analysis. The increasing awareness of population, the burden of new types of disease, as well as the recurrence of food scandals have recently launched a scientific and population debate on the contribution of foods items, especially those of animal origin, to the toxic exposure of food producing animals and humans. This paper critically reviews the occurrence of toxicants in most consumed foods of animal origin in Cameroon. This study included the most consumed food of animal origin, identified during the national household budget survey and contributing to 8.1% of the total diet of an individual. Data evaluated suggest an important contamination by toxic metals, mycotoxins, veterinary drugs’ residues, and pesticides. The current national legal framework is briefly analyzed to explore possible intervention measures in the frame of the One Health approach.

  15. Anticoagulant rodenticide toxicity to non-target wildlife under controlled exposure conditions

    Science.gov (United States)

    Rattner, Barnett A.; Mastrota, F. Nicholas; van den Brink, Nico; Elliott, J.; Shore, R.; Rattner, B.

    2018-01-01

    Much of our understanding of anticoagulant rodenticide toxicity to non-target wildlife has been derived from molecular through whole animal research and registration studies in domesticated birds and mammals, and to a lesser degree from trials with captive wildlife. Using these data, an adverse outcome pathway identifying molecular initiating and anchoring events (inhibition of vitamin K epoxide reductase, failure to activate clotting factors), and established and plausible linkages (coagulopathy, hemorrhage, anemia, reduced fitness) associated with toxicity, is presented. Controlled exposure studies have demonstrated that second-generation anticoagulant rodenticides (e.g., brodifacoum) are more toxic than first- and intermediate-generation compounds (e.g., warfarin, diphacinone), however the difference in potency is diminished when first- and intermediate-generation compounds are administered on multiple days. Differences in species sensitivity are inconsistent among compounds. Numerous studies have compared mortality rate of predators fed prey or tissue containing anticoagulant rodenticides. In secondary exposure studies in birds, brodifacoum appears to pose the greatest risk, with bromadiolone, difenacoum, flocoumafen and difethialone being less hazardous than brodifacoum, and warfarin, coumatetralyl, coumafuryl, chlorophacinone and diphacinone being even less hazardous. In contrast, substantial mortality was noted in secondary exposure studies in mammals ingesting prey or tissue diets containing either second- or intermediate-generation compounds. Sublethal responses (e.g., prolonged clotting time, reduced hematocrit and anemia) have been used to study the sequelae of anticoagulant intoxication, and to some degree in the establishment of toxicity thresholds or toxicity reference values. Surprisingly few studies have undertaken histopathological evaluations to identify cellular lesions and hemorrhage associated with anticoagulant rodenticide exposure in non

  16. Toxicity assessment of industrial chemicals and airborne contaminants: transition from in vivo to in vitro test methods: a review.

    Science.gov (United States)

    Bakand, S; Winder, C; Khalil, C; Hayes, A

    2005-12-01

    Exposure to occupational and environmental contaminants is a major contributor to human health problems. Inhalation of gases, vapors, aerosols, and mixtures of these can cause a wide range of adverse health effects, ranging from simple irritation to systemic diseases. Despite significant achievements in the risk assessment of chemicals, the toxicological database, particularly for industrial chemicals, remains limited. Considering there are approximately 80,000 chemicals in commerce, and an extremely large number of chemical mixtures, in vivo testing of this large number is unachievable from both economical and practical perspectives. While in vitro methods are capable of rapidly providing toxicity information, regulatory agencies in general are still cautious about the replacement of whole-animal methods with new in vitro techniques. Although studying the toxic effects of inhaled chemicals is a complex subject, recent studies demonstrate that in vitro methods may have significant potential for assessing the toxicity of airborne contaminants. In this review, current toxicity test methods for risk evaluation of industrial chemicals and airborne contaminants are presented. To evaluate the potential applications of in vitro methods for studying respiratory toxicity, more recent models developed for toxicity testing of airborne contaminants are discussed.

  17. Virgin coconut oil supplementation ameliorates cyclophosphamide-induced systemic toxicity in mice.

    Science.gov (United States)

    Nair, S S; Manalil, J J; Ramavarma, S K; Suseela, I M; Thekkepatt, A; Raghavamenon, A C

    2016-02-01

    Virgin coconut oil (VCO) is an unrefined kernal oil, prepared from Cocos nucifera L., having substantial nutritional and medicinal value. Experimental studies have suggested its antioxidant, anti-inflammatory, immunostimulatory and hypolipidemic effects. The present study assesses its effect on formalin-induced chronic inflammation and cyclophosphamide (CTX)-induced systemic toxicity in murine models. Oral administration of VCO effectively reduced formalin-induced paw oedema in mice with more or less similar efficacy as that of diclofenac. The CTX-induced hike in blood urea, creatinine, thiobarbituric acid reactive substances (TBARS) and liver marker enzymes in mice was marginally decreased by VCO (8 g/kg body weight) ingestion orally. The liver and kidney catalase, superoxide dismutase and glutathione peroxidase activities, together with cellular glutathione and TBARS levels, were found to be improved in these animals. Overall the study reveals the protective efficacy of VCO against secondary toxicity induced by CTX possibly through its antioxidant and anti-inflammatory properties. © The Author(s) 2015.

  18. Flaws in animal studies exploring statins and impact on meta-analysis.

    Science.gov (United States)

    Moja, Lorenzo; Pecoraro, Valentina; Ciccolallo, Laura; Dall'Olmo, Luigi; Virgili, Gianni; Garattini, Silvio

    2014-06-01

    Animal experiments should be appropriately designed, correctly analysed and transparently reported to increase their scientific validity and maximise the knowledge gained from each experiment. This systematic review of animal experiments investigating statins evaluates their quality of reporting and methodological aspects as well as their implications for the conduction of meta-analyses. We searched medline and embase for studies reporting research on statins in mice, rats and rabbits. We collected detailed information about the characteristics of studies, animals and experimental methods. We retrieved 161 studies. A little over half did not report randomisation (55%) and most did not describe blinding (88%). All studies reported details on the experimental procedure, although many omitted information about animal gender, age or weight. Four percent did not report the number of animals used. None reported the sample size. Fixed- and random-effects models gave different results (ratio of effect size increased by five folds). Heterogeneity was consistently substantial within animal models, for which accounting for covariates had minimal impact. Publication bias is highly suspected across studies. Although statins showed efficacy in animal models, preclinical studies highlighted fundamental problems in the way in which such research is conducted and reported. Results were often difficult to interpret and reproduce. Different meta-analytic approaches were highly inconsistent: a reliable approach to estimate the true parameter was imperceptible. Policies that address these issues are required from investigators, editors and institutions that care about the quality standards and ethics of animal research. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

  19. Lead in soils, plants and animals

    Energy Technology Data Exchange (ETDEWEB)

    Scheltinga, H

    1955-01-01

    The toxicity of lead for plants is small, except in the case of water cultures. Animals can absorb more lead without toxic effect than was previously expected. This applies to acute poisoning as well as chronic poisoning. As a result of experiments over many years (Allcroft and Blaxter, 1950) the possibility of chronic lead poisoning has been found to be minute. Rations containing 240 mg lead/kg dried fodder, given daily over a period of three years, did not cause any poisoning at all in cattle thus fed. Where lead poisoning did take place, it was observed that the ratio of lead in the dried fodder was > 1000 mg/kg; the proportion was generally much higher. In normal cases grass contains only 5 to 15 mg lead/kg. The total lead content of samples from arable land was 10 to 25 mg/kg soil. For grassland on peat or clay the amount was slightly higher. The influence on the lead status of soils and plants of fertilizing with compost or copper slag flour, both containing a small percentage of lead, proved to be negligible. It is definite that in normal use, these fertilizers cannot cause any danger for either plant or animal. 24 references, 3 tables.

  20. Dermal and inhalation acute toxic class methods: test procedures and biometric evaluations for the Globally Harmonized Classification System.

    Science.gov (United States)

    Holzhütter, H G; Genschow, E; Diener, W; Schlede, E

    2003-05-01

    The acute toxic class (ATC) methods were developed for determining LD(50)/LC(50) estimates of chemical substances with significantly fewer animals than needed when applying conventional LD(50)/LC(50) tests. The ATC methods are sequential stepwise procedures with fixed starting doses/concentrations and a maximum of six animals used per dose/concentration. The numbers of dead/moribund animals determine whether further testing is necessary or whether the test is terminated. In recent years we have developed classification procedures for the oral, dermal and inhalation routes of administration by using biometric methods. The biometric approach assumes a probit model for the mortality probability of a single animal and assigns the chemical to that toxicity class for which the best concordance is achieved between the statistically expected and the observed numbers of dead/moribund animals at the various steps of the test procedure. In previous publications we have demonstrated the validity of the biometric ATC methods on the basis of data obtained for the oral ATC method in two-animal ring studies with 15 participants from six countries. Although the test procedures and biometric evaluations for the dermal and inhalation ATC methods have already been published, there was a need for an adaptation of the classification schemes to the starting doses/concentrations of the Globally Harmonized Classification System (GHS) recently adopted by the Organization for Economic Co-operation and Development (OECD). Here we present the biometric evaluation of the dermal and inhalation ATC methods for the starting doses/concentrations of the GHS and of some other international classification systems still in use. We have developed new test procedures and decision rules for the dermal and inhalation ATC methods, which require significantly fewer animals to provide predictions of toxicity classes, that are equally good or even better than those achieved by using the conventional LD(50)/LC

  1. [Specific features of 2-methyl hydroxybenzene and 3-methyl hydroxybenzene distribution in the organism of warm-blooded animals].

    Science.gov (United States)

    Shormanov, B K; Grishenko, V K; Astashkina, A P; Elizarova, M K

    2013-01-01

    The present work was designed to study the specific features of 2-methyl hydroxybezene and 3-methyl hydroxybenzene distribution after intragastric administration of these toxicants to warm-blooded animals (rats). They were detected in the unmetabolized form in the internal organs and blood of the animals. The levels of 2-methyl hydroxybezene were especially high in the stomach and blood whereas the maximum content of 3-methyl hydroxybenzene was found in brain, blood, small intestines of the poisoned rats.

  2. QSAR models for reproductive toxicity and endocrine disruption in regulatory use – a preliminary investigation

    DEFF Research Database (Denmark)

    Jensen, Gunde Egeskov; Niemelä, Jay Russell; Wedebye, Eva Bay

    2008-01-01

    the new legislation. This article focuses on a screening exercise by use of our own and commercial QSAR models for identification of possible reproductive toxicants. Three QSAR models were used for reproductive toxicity for the endpoints teratogenic risk to humans (based on animal tests, clinical data...... for humans owing to possible developmental toxic effects: Xn (Harmful) and R63 (Possible risk of harm to the unborn child). The chemicals were also screened in three models for endocrine disruption....

  3. Survey the frequency and type of Fungal Contaminants in Animal Feed of Yazd Dairy Cattles

    Directory of Open Access Journals (Sweden)

    mohammad taghi ghaneian

    2016-04-01

    Full Text Available Introduction About 500,000 species of fungi have been realized up to now. There are abundant fungi in air, soil and our environment. So the growth of them increases in the presence of air moisture and appropriate temperature. However saprophytic fungi have a wide distribution in nature, they are responsible for decomposition of organic materials and playing an important role in the biogeochemical cycles of major nutrients. Some saprophytes are toxic that contaminate human foods and animal feeds by production of mycotoxins. Aflatoxins are the most common and dangerous mycotoxins produced by few species of Aspergillus and penicillium. This group of mycotoxin has disorder and risks, including the induction of liver cancer. They are mutagenic and teratogenic. Aflatoxin B1, B2, G1 and G2, which are naturally produced by several toxic fungi, may contaminate a wide range of dairy animal feeds resulted severe economic loss of cattle meat. Since Aflatoxin B1 and B2 can be transmitted via mammalian’s milk and cheese in form of synthetic Aflatoxin M1 and M2 to human consumers, cause significant health problems. Therefore contamination of animal feed with common toxic airborne saprophytic fungi is a major concern of health officials. Wheat, barley, corn, soybean and other animal feeds may be contaminated with toxic fungi during implantation, harvesting and storage. There are many dairy and livestock centers in Yazd that prepare milk and dairy products for Yazd and neighboring provinces. The aim of current study was to evaluate the amount and type of fungal contaminates of dairy feeds in Yazd dairies. Materials and methods This cross-sectional descriptive study was conducted in the summer of 2012 on 23 dairies in Yazd. Samples of different animal feeds including concentrates, wheat straw, hay, corn, silage corn, soybean and canola as well as waste of bread, were randomly selected from their bulks. The temperature and humidity of feed storage were recorded

  4. A Study on the D. magna and V. fischeri Toxicity Relationship of Industrial Wastewater from Korea

    Science.gov (United States)

    Pyo, S.; Lee, S.; Chun Sang, H.; Park, T. J.; Kim, M. S.

    2015-12-01

    It is well known that high concentration of TDS (total dissolved solid) in industrial effluent gives rise to the toxicity to the Daphnia magna toxicity test. D. magna is vulnerable to relatively low TDS concentration showing the 24-hr EC50 of Salinity 0.6% (as the sea salt concentration). Recently, standard mandatory toxicity testing using Daphnia magna has been used to monitor industrial effluent toxicity according to Korea standard method (Acute Toxicity Test Method of the Daphnia magna Straus (Cladocera, Crustacea), ES 04704. 1a) under regulation. Since only one acute toxicity testing is applied in the present, we are trying to introduce microbial battery for more complete toxicity assessment. In this study, the acute toxicities between daphnids and microbes were compared. The results of D. magna and Vibrio fischeri toxicity test from 165 industrial wastewater effluents showed high positive correlation. In addition, the possibility of predicting daphnia toxicity from the bacterial toxicity data amounts to 92.6% if we consider salinity effect (>5ppt) together. From this study, we found that the V. fischeri toxicity test is a powerful battery tool to assess the industrial wastewater toxicity. Here, we suggest that luminescent bacteria toxicity test be useful not only for complete toxicity assessment which can't be obtained by daphnia toxicity testing only but also for the reduction cost, time, and labor in the Korean society. Keywords : D. magna, V. fischeri, Industrial waste water, battery test Acknowledgement This research was supported by a grant (15IFIP-B089908-02) from Plant Research Program funded by Ministry of Land, Infrastructure and Transport of Korean government

  5. Small Animal [18F]FDG PET Imaging for Tumor Model Study

    International Nuclear Information System (INIS)

    Woo, Sang Keun; Kim, Kyeong Min; Cheon, Gi Jeong

    2008-01-01

    PET allows non-invasive, quantitative and repetitive imaging of biological function in living animals. Small animal PET imaging with [ 18 F]FDG has been successfully applied to investigation of metabolism, receptor, ligand interactions, gene expression, adoptive cell therapy and somatic gene therapy. Experimental condition of animal handling impacts on the biodistribution of [ 18 F]FDG in small animal study. The small animal PET and CT images were registered using the hardware fiducial markers and small animal contour point. Tumor imaging in small animal with small animal [ 18 F]FDG PET should be considered fasting, warming, and isoflurane anesthesia level. Registered imaging with small animal PET and CT image could be useful for the detection of tumor. Small animal experimental condition of animal handling and registration method will be of most importance for small lesion detection of metastases tumor model

  6. Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L).

    Science.gov (United States)

    Liju, Vijayasteltar B; Jeena, Kottarapat; Kuttan, Ramadasan

    2013-03-01

    The present study investigated the acute, subchronic and genotoxicity of turmeric essential oil (TEO) from Curcuma longa L. Acute administration of TEO was done as single dose up to 5 g of TEO per kg body weight and subchronic toxicity study for thirteen weeks was done by daily oral administration of TEO at doses 0.1, 0.25 and 0.5 g/kg b.wt. in Wistar rats. There were no mortality, adverse clinical signs or changes in body weight; water and food consumption during acute as well as subchronic toxicity studies. Indicators of hepatic function such as aspartate aminotransferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were unchanged in treated animals compared to untreated animals. Oral administration of TEO for 13 weeks did not alter total cholesterol, triglycerides, markers of renal function, serum electrolyte parameters and histopathology of tissues. TEO did not produce any mutagenicity to Salmonella typhimurium TA-98, TA-100, TA-102 and TA-1535 with or without metabolic activation. Administration of TEO to rats (1 g/kg b.wt.) for 14 days did not produce any chromosome aberration or micronuclei in rat bone marrow cells and did not produce any DNA damage as seen by comet assay confirming the non toxicity of TEO. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. The Netherlands XTC Toxicity (NeXT) study: objectives and methods of a study investigating causality, course, and clinical relevance

    NARCIS (Netherlands)

    de Win, Maartje M. L.; Jager, Gerry; Vervaeke, Hylke K. E.; Schilt, Thelma; Reneman, Liesbeth; Booij, Jan; Verhulst, Frank C.; den Heeten, Gerard J.; Ramsey, Nick F.; Korf, Dirk J.; van den Brink, Wim

    2005-01-01

    This paper describes the objectives and methods of The Netherlands XTC Toxicity (NeXT) study focussing on the causality, course, and clinical relevance of ecstasy neurotoxicity. Previous studies suggest that ecstasy (3,4 methylene-dioxymethamphetamine, MDMA, XTC) is toxic toward brain serotonin

  8. The ChemScreen project to design a pragmatic alternative approach to predict reproductive toxicity of chemicals

    DEFF Research Database (Denmark)

    van der Burg, Bart; Wedebye, Eva Bay; Dietrich, Daniel R.

    2015-01-01

    to validate the test panel using mechanistic approaches. We are actively engaged in promoting regulatory acceptance of the tools developed as an essential step towards practical application, including case studies for read-across purposes. With this approach, a significant saving in animal use and associated......There is a great need for rapid testing strategies for reproductive toxicity testing, avoiding animal use. The EU Framework program 7 project ChemScreen aimed to fill this gap in a pragmatic manner preferably using validated existing tools and place them in an innovative alternative testing...

  9. Physiology and toxicity of fluoride

    OpenAIRE

    Dhar Vineet; Bhatnagar Maheep

    2009-01-01

    Fluoride has been described as an essential element needed for normal development and growth of animals and extremely useful for human beings. Fluoride is abundant in the environment and the main source of fluoride to humans is drinking water. It has been proved to be beneficial in recommended doses, and at the same time its toxicity at higher levels has also been well established. Fluoride gets accumulated in hard tissues of the body and has been know to play an important role in mineralizat...

  10. A study of the anti-inflammatory effect of the leaves of Psidium guajava Linn. on experimental animal models

    Science.gov (United States)

    Dutta, Sarmistha; Das, Swarnamoni

    2010-01-01

    Introduction: The aim is to study the anti-inflammatory effect of the ethanolic extract of the leaves of Psidium guajava(PGE) on experimental animal models. Materials and Methods: Fresh leaves were collected, air-dried, powdered, and percolated in 95% ethanol. Acute toxicity test was done according to OECD guidelines. Four groups of animals of either sex, weighing 150–200g of the species Rattus norvegicus were taken for the study (n = 6). Group A was taken as control (3% gum acacia in 10 mL/kg body weight), Group B as test group (PGE 250 mg/kg body weight), Group C as test group (PGE 500 mg/kg body weight), and Group D as standard (Aspirin 100 mg/kg body weight). The animals were studied for acute inflammation by Carrageenan-induced rat paw edema, subacute inflammation by Granuloma pouch method, and chronic inflammation by Freund’s adjuvant-induced arthritis method. Statistical analysis was done by one-way analysis of variance followed by multiple comparison tests. Results: In acute inflammation, there was significant inhibition of paw edema in Groups B, C, and D in comparison with Group A (P < 0.05). In subacute inflammation, there was significant inhibition of exudate formation in Groups B, C, and D in comparison to Group A (P < 0.05). In chronic inflammation, there was significant inhibition of paw edema and inhibition of weight reduction in Groups B, C, and D compared with Group A. Downregulation of arthritis index was also significant in Groups B, C, and D in comparison with Group A (P < 0.05). Conclusion: The ethanolic extract of PGE has significant anti-inflammatory activity. PMID:21589759

  11. PCBs and PCDD/Fs distribution in tissues and organs of marine animals in Russian Arctic

    Energy Technology Data Exchange (ETDEWEB)

    Amirova, Z.; Kruglov, E.; Loshkina, E.; Khalilov, R. [Environmental Research and Protection Centre, Ufa (Russian Federation); Melnikov, S.; Vlasov, S. [Regional Centre Monitoring of the Arctic, St. Petersburg (Russian Federation)

    2004-09-15

    Studies of persistent organic pollutants (POPs) in the Russian Arctic were conducted recently by a Arctic Monitoring and Assessment Program (AMAP) project. This project developed new data on the POPs pollution levels in the environment and biosphere, including PCBs and PCDD/Fs, in arctic regions of Russia. Transboundary transport and biomagnification within food chains in arctic regions result in POPs accumulation in tissues of fish and marine animals. The aim of this study was to determine the concentration of indicator PCBs, co-planar PCBs and PCDD/Fs in different tissues and organs of seals, walruses and whales caught near the seashore of Chukotski Peninsula (settlement of Lavrenty), Russia, to determine the background level of arctic biota pollution and to study distribution of toxicants in organisms of marine animals. Sampling was made in the course of the 1{sup st} and the 2{sup nd} stages of the 4{sup th} phase of Raipon/AMAP/GEF project ''Persistent Toxic Substances (PTS), Food Security and Indigenous Peoples of the Russian North'' in 2002 by researchers of the Regional Center for Monitoring of the Arctic (RCMA), St. Petersburg, Russia.

  12. Toxicity levels to humans during acute exposure to hydrogen fluoride

    International Nuclear Information System (INIS)

    Halton, D.M.; Dranitsaris, P.; Baynes, C.J.

    1984-11-01

    A literature review was conducted of the acute toxicity of hydrogen fluoride (HF) with emphasis on the effects of inhalation of gaseous HF. The data and findings of the relevant references were summarized under four categories: animal studies, controlled human studies, community exposure and industrial exposure. These were critically reviewed and then lethal concentration-time relationships were developed for humans, corresponding to LCsub(LO), LCsub(10) and LCsub(50) levels. The effects of age, health and other physiological variables on the sensitivity to HF were discussed, as well as antagonistic and synergistic effects with other substances

  13. Pharmacological Effects of Biotin in Animals.

    Science.gov (United States)

    Riveron-Negrete, Leticia; Fernandez-Mejia, Cristina

    2017-01-01

    In recent decades, it was found that vitamins affect biological functions in ways other than their long-known functions; niacin is the best example of a water-soluble vitamin known to possess multiple actions. Biotin, also known as vitamin B7 or vitamin H, is a water-soluble B-complex vitamin that serves as a covalently-bound coenzyme of carboxylases. It is now well documented that biotin has actions other than participating in classical enzyme catalysis reactions. Several lines of evidence have demonstrated that pharmacological concentrations of biotin affect glucose and lipid metabolism, hypertension, reproduction, development, and immunity. The effect of biotin on these functions is related to its actions at the transcriptional, translational, and post-translational levels. The bestsupported mechanism involved in the genetic effects of biotin is the soluble guanylate cyclase/protein kinase G (PKG) signaling cascade. Although there are commercially-available products containing pharmacological concentrations of biotin, the toxic effects of biotin have been poorly studied. This review summarizes the known actions and molecular mechanisms of pharmacological doses of biotin in animals and current information regarding biotin toxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. GMP-grade α-TEA lysine salt: a 28-Day oral toxicity and toxicokinetic study with a 28-Day recovery period in Beagle dogs

    International Nuclear Information System (INIS)

    Guerrouahen, Bella S.; Hahn, Tobias; Alderman, Zefora; Curti, Brendan; Urba, Walter; Akporiaye, Emmanuel T.

    2016-01-01

    Alpha-tocopheryloxyacetic acid (α-TEA) is a semi-synthetic derivative of naturally occurring vitamin E (alpha-tocopherol) that can be delivered via an oral route. Preclinical in vitro and in vivo data demonstrated that α-TEA is a potent anti-tumor agent with a safe toxicity profile in mice. We report a comprehensive study to evaluate the toxokinetics of good manufacturing practice (GMP)-grade α-TEA in dogs after daily oral administration for 28 days, followed by a 28-day recovery period. Male and female beagle dogs received capsules of α-TEA Lysine Salt at doses of 100, 300, 1500 mg/kg/day. α-TEA plasma levels were determined by high-performance liquid chromatography (HPLC) with mass spectrometric detection. During the treatment, animals were observe for clinical signs, food consumption, body weight, and subjected to ophthalmoscopic, and electrocardiographic assessments. At the end of the dosing period, blood was taken and toxicokinetic analyses and histopathology assessments were performed when animals were necropsied. Our findings showed that there was no α-TEA-related mortality or moribundity. At the highest dose, increases in white blood cells and fibrinogen levels were observed. These levels returned to normal at the end of the recovery period. Histopathological evaluation of major organs revealed no significant lesions related to α-TEA-treatment. We demonstrate that for designing clinical trials in patients, the highest non-severely toxic dose (HNSTD) of α-TEA is 1500 mg/kg/day in Beagle dogs and this data informed the design of dose-escalation studies of α-TEA in patients with advanced cancer

  15. The evolution of juvenile animal testing for small and large molecules.

    Science.gov (United States)

    Baldrick, Paul

    2013-11-01

    Recent formalised regulatory requirements for ensuring safe use of new drugs in children has increased the requirement, when considered relevant, to perform juvenile animal testing before commencing paediatric clinical trials. A key goal of this work is to identify or examine for a developmental or toxicity finding not seen in other toxicology testing. With our current knowledge, this paper examines what types of testing are occurring, what novel findings are being seen and their relevance in the safety evaluation process. Furthermore, trends for now and the future in the type of juvenile animal testing will be described including a need for more focused study designs and more published data on modern cross-species postnatal development. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Toxicity of palmitoyl glycerol to mice: depression of thyroid function

    International Nuclear Information System (INIS)

    Trumbo, P.R.; Meuten, D.J.; King, M.W.; Tove, S.B.

    1987-01-01

    Mice given propylthiouracil, a thyroid inhibitor, and fed a diet containing a nontoxic level of rac-1(3)-palmitoyl glycerol showed the hypothermia and mortality expected for a toxic dose, but did not show these signs when linoleate or oleate was added to the diet. Loss of radioiodine from the whole animal and thyroid gland was slower when mice were fed the toxic palmitoyl glycerol diet than when fed the same diet containing 4% safflower oil. However, mice fed the two diets did not differ in the extent of the incorporation of radioiodine, and essentially all was bound to protein in each case. Follicular thyroid cells from mice fed the potentially toxic diet that contained unsaturated fat were normal in appearance. Conversely, cells from mice fed the toxic diet were smaller and more densely stained, showing evidence of glycoprotein inside the cell. These findings show that the thyroid gland is affected by the palmitoyl glycerol diet. However, the thyroid is not the only organ affected, because giving either thyroxine or triiodothyronine had no effect on the toxicity of palmitoyl glycerol

  17. Can results from animal studies be used to estimate dose or low-dose effects in humans

    International Nuclear Information System (INIS)

    Thomas, J.M.; Eberhardt, L.L.

    1980-09-01

    A method has been developed based on animal data which appears useful in predicting biological equilibrium level for radionuclides in humans. It is shown that measures of whole-body retention, plasma concentration, short-term toxicity and cancer incidence can be projected, at least in limited circumstances, for some elements and organic compounds. Some of the procedures used for extrapolation in other fields as well as those from radiobiology are reviewed, the similarity procedure developed discussed, and a review provided of some of the issues in low-dose-effect modelling and the extrapolation of those data to humans

  18. Toxicity of fluoride to aquatic species and evaluation of toxicity modifying factors.

    Science.gov (United States)

    Pearcy, Krysta; Elphick, James; Burnett-Seidel, Charlene

    2015-07-01

    The present study was performed to investigate the toxicity of fluoride to a variety of freshwater aquatic organisms and to establish whether water quality variables contribute substantively to modifying its toxicity. Water hardness, chloride, and alkalinity were tested as possible toxicity modifying factors for fluoride using acute toxicity tests with Hyalella azteca and Oncorhynchus mykiss. Chloride appeared to be the major toxicity modifying factor for fluoride in these acute toxicity tests. The chronic toxicity of fluoride was evaluated with a variety of species, including 3 fish (Pimephales promelas, O. mykiss, and Salvelinus namaycush), 3 invertebrates (Ceriodaphnia dubia, H. azteca, and Chironomus dilutus), 1 plant (Lemna minor), and 1 alga (Pseudokirchneriella subcapitata). Hyalella azteca was the most sensitive species overall, and O. mykiss was the most sensitive species of fish. The role of chloride as a toxicity modifying factor was inconsistent between species in the chronic toxicity tests. © 2015 SETAC.

  19. The use of pig hepatocytes for biotransformation and toxicity studies

    NARCIS (Netherlands)

    Hoogenboom, L.A.P.

    1991-01-01

    The three main objectives of this study were, (1) to investigate the possibility to isolate viable hepatocytes from liver samples of pigs, (2) to study their use for biotransformation and toxicity studies, and (3) to demonstrate the value of this model, in particular in the field of residue

  20. Oxytetracycline induces DNA damage and epigenetic changes: a possible risk for human and animal health?

    Science.gov (United States)

    Gallo, Adriana; Landi, Rosaria; Rubino, Valentina; Di Cerbo, Alessandro; Giovazzino, Angela; Palatucci, Anna Teresa; Centenaro, Sara; Guidetti, Gianandrea; Canello, Sergio; Cortese, Laura; Ruggiero, Giuseppina; Alessandrini, Andrea; Terrazzano, Giuseppe

    2017-01-01

    Oxytetracycline (OTC), which is largely employed in zootechnical and veterinary practices to ensure wellness of farmed animals, is partially absorbed within the gastrointestinal tract depositing in several tissues. Therefore, the potential OTC toxicity is relevant when considering the putative risk derived by the entry and accumulation of such drug in human and pet food chain supply. Despite scientific literature highlights several OTC-dependent toxic effects on human and animal health, the molecular mechanisms of such toxicity are still poorly understood. Here, we evaluated DNA damages and epigenetic alterations by quantitative reverse transcription polymerase chain reaction, quantitative polymerase chain reaction, chromatin immuno-precipitation and Western blot analysis. We observed that human peripheral blood mononuclear cells (PBMCs) expressed DNA damage features (activation of ATM and p53, phosphorylation of H2AX and modifications of histone H3 methylation of lysine K4 in the chromatin) after the in vitro exposure to OTC. These changes are linked to a robust inflammatory response indicated by an increased expression of Interferon (IFN)- γ and type 1 superoxide dismutase (SOD1). Our data reveal an unexpected biological in vitro activity of OTC able to modify DNA and chromatin in cultured human PBMC. In this regard, OTC presence in foods of animal origin could represent a potential risk for both the human and animal health.

  1. Interactions between toxic chemicals and natural environmental factors--a meta-analysis and case studies.

    Science.gov (United States)

    Laskowski, Ryszard; Bednarska, Agnieszka J; Kramarz, Paulina E; Loureiro, Susana; Scheil, Volker; Kudłek, Joanna; Holmstrup, Martin

    2010-08-15

    The paper addresses problems arising from effects of natural environmental factors on toxicity of pollutants to organisms. Most studies on interactions between toxicants and natural factors, including those completed in the EU project NoMiracle (Novel Methods for Integrated Risk Assessment of Cumulative Stressors in Europe) described herein, showed that effects of toxic chemicals on organisms can differ vastly depending purely on external conditions. We compiled data from 61 studies on effects of temperature, moisture and dissolved oxygen on toxicity of a range of chemicals representing pesticides, polycyclic aromatic hydrocarbons, plant protection products of bacterial origin and trace metals. In 62.3% cases significant interactions (pnatural factors and chemicals were found, reaching 100% for the effect of dissolved oxygen on toxicity of waterborne chemicals. The meta-analysis of the 61 studies showed that the null hypothesis assuming no interactions between toxic chemicals and natural environmental factors should be rejected at p=2.7 x 10(-82) (truncated product method probability). In a few cases of more complex experimental designs, also second-order interactions were found, indicating that natural factors can modify interactions among chemicals. Such data emphasize the necessity of including information on natural factors and their variation in time and across geographic regions in ecological risk assessment. This can be done only if appropriate ecotoxicological test designs are used, in which test organisms are exposed to toxicants at a range of environmental conditions. We advocate designing such tests for the second-tier ecological risk assessment procedures. Copyright 2010 Elsevier B.V. All rights reserved.

  2. Toxicоlogical evaluation of the plant products using Brine Shrimp (Artemia salina L. model

    Directory of Open Access Journals (Sweden)

    Меntor R. Hamidi

    2014-04-01

    Full Text Available Many natural products could serve as the starting point in the development of modern medicines because of their numerous biological and pharmacological activities. However, some of them are known to carry toxicological properties as well. In order to achieve a safe treatment with plant products, numerous research studies have recently been focused on both pharmacology and toxicity of medicinal plants. Moreover, these studies employed efforts for alternative biological assays. Brine Shrimp Lethality Assay is the most convenient system for monitoring biological activities of various plant species. This method is very useful for preliminary assessment of toxicity of the plant extracts. Rapidness, simplicity and low requirements are several advantages of this assay. However, several conditions need to be completed, especially in the means of standardized experimental conditions (temperature, pH of the medium, salinity, aeration and light. The toxicity of herbal extracts using this assay has been determined in a concentration range of 10, 100 and 1000 µg/ml of the examined herbal extract. Most toxicity studies which use the Brine Shrimp Lethality Assay determine the toxicity after 24 hours of exposure to the tested sample. The median lethal concentration (LC50 of the test samples is obtained by a plot of percentage of the dead shrimps against the logarithm of the sample concentration. LC50 values are estimated using a probit regression analysis and compared with either Meyer’s or Clarkson’s toxicity criteria. Furthermore, the positive correlation between Meyer’s toxicity scale for Artemia salina and Gosselin, Smith and Hodge’s toxicity scale for higher animal models confirmed that the Brine Shrimp Lethality Assay is an excellent predictive tool for the toxic potential of plant extracts in humans.

  3. Four-week oral toxicity study with erythritol in rats

    NARCIS (Netherlands)

    Til, H.P.; Modderman, J.

    1996-01-01

    Erythritol was orally administered to Wistar rats at dietary levels of 0, 5, and 10% for 4 weeks. Soft stools and diarrhea were observed in male and female animals of the 10% group and in female animals of the 5% group. These symptoms disappeared during the course of the study. Mean body weights of

  4. Toxicity of strontium-90 depending on the way of its administration to animal organisms

    International Nuclear Information System (INIS)

    Shvedov, V.L.

    1978-01-01

    Toxicity of strontium-90 administered orally is almost thrice lower than that after parenteral administration. The values of the doses absorbed in the critical organ of rats, corresponding to LDsub(50/30), were 2400 to 2600 rad irrespective of the route of the radionuclide administration

  5. Present state of research in Japan on toxicities of gases during fire

    Science.gov (United States)

    Kishitani, K.; Saito, F.; Yusa, S.

    Research on toxicities of gases during fire and gas toxicity experiments using animals conducted in full size fire tests is reported. The following tests were conducted: (1) analyses of formaldehyde, acrolein, and HCN; (2) analyses of smoke particulates; and (3) types and rates of generation of combustion products, and the investigation of the relationship between CO and CO2 generation and combustion conditions. The relationship between conditions of maximum emission of CO and CO2 is also investigated.

  6. Comparison of the therapeutic effect between sodium bicarbonate and insulin on acute propafenone toxicity.

    Science.gov (United States)

    Yi, Hwa Yeon; Lee, Jang Young; Lee, Won Suk; Sung, Won Young; Seo, Sang Won

    2014-10-01

    Unlike other sodium-channel-blocking antiarrhythmic agents, propafenone has β-blocking effects and calcium-channel-blocking effects. Yi et al recently studied insulin's treatment effect on acute propafenone toxicity in rats. However, because the degree of effectiveness of insulin compared to the previously known antidote sodium bicarbonate (NaHCO3) was not studied, the 2 treatment methods were compared for propafenone intoxication in rats. Rats received intravenous propafenone (36 mg/[kg h]) for 12 minutes. After the induction of toxicity, rats (n = 10 per group) received normal saline solution (NSS), NaHCO3, or insulin with glucose as treatment. Animals in the NSS, NaHCO3, and Insulin groups received an intravenous infusion of 36 mg/(kg h) propafenone until death occurred. For each animal, the mean arterial pressure (MAP, heart rate, PR interval, QRS duration, total hemoglobin, sodium, potassium, potential of hydrogen, bicarbonate, glucose, lactate, and central venous oxygen saturation (Scvo2) were measured and compared among the groups. Survival of the Insulin group was greater than that of the NSS group by log-rank test (P = .021). Sodium bicarbonate prevented the decline of MAP for 55 minutes. In comparison, insulin prevented the decline of MAP and heart rate, and the elongation of the PR interval and QRS duration for 55 minutes (P < .05). Propafenone toxicity led to decreased Ca(2+), potential of hydrogen, and Scvo2 and increased lactate levels. Insulin prevented the decrease of Ca(2+) and Scvo2, whereas NaHCO3 prevented the increase in lactate. Insulin treatment was more effective than NaHCO3 on acute propafenone toxicity in rat. Therefore, when propafenone-induced cardiotoxicity occurs, which is unresponsive to current treatment methods, glucose-insulin infusion may be considered. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Monitoring residue in animals and primary products of animal origin

    Directory of Open Access Journals (Sweden)

    Janković Saša

    2008-01-01

    Full Text Available The objective of control and systematic monitoring of residue is to secure, by the examination of a corresponding number of samples, the efficient monitoring of the residue level in tissues and organs of animals, as well as in primary products of animal origin. This creates possibilities for the timely taking of measures toward the securing of food hygiene of animal origin and the protection of public health. Residue can be a consequence of the inadequate use of medicines in veterinary medicine and pesticides in agriculture and veterinary medicine, as well as the polluting of the environment with toxic elements, dioxins, polychlorinated biphenyls, and others. Residue is being monitored in Serbia since 1972, and in 2004, national monitoring was brought to the level of EU countries through significant investments by the Ministry of Agriculture, Forestry and Water Management. This is also evident in the EU directives which permit exports of all kinds of meat and primary products of animal origin, covered by the Residue Monitoring Program. The program of systematic examinations of residue has been coordinated with the requirements of the European Union, both according to the type of examined substance, as well as according to the number of samples and the applied analytical techniques. In addition to the development of methods and the including of new harmful substances into the monitoring programme, it is also necessary to coordinate the national regulations that define the maximum permitted quantities of certain medicines and contaminants with the EU regulations, in order to protect the health of consumers as efficiently as possible, and for the country to take equal part in international trade.

  8. The margin of internal exposure (MOIE) concept for dermal risk assessment based on oral toxicity data - A case study with caffeine.

    Science.gov (United States)

    Bessems, Jos G M; Paini, Alicia; Gajewska, Monika; Worth, Andrew

    2017-12-01

    Route-to-route extrapolation is a common part of human risk assessment. Data from oral animal toxicity studies are commonly used to assess the safety of various but specific human dermal exposure scenarios. Using theoretical examples of various user scenarios, it was concluded that delineation of a generally applicable human dermal limit value is not a practicable approach, due to the wide variety of possible human exposure scenarios, including its consequences for internal exposure. This paper uses physiologically based kinetic (PBK) modelling approaches to predict animal as well as human internal exposure dose metrics and for the first time, introduces the concept of Margin of Internal Exposure (MOIE) based on these internal dose metrics. Caffeine was chosen to illustrate this approach. It is a substance that is often found in cosmetics and for which oral repeated dose toxicity data were available. A rat PBK model was constructed in order to convert the oral NOAEL to rat internal exposure dose metrics, i.e. the area under the curve (AUC) and the maximum concentration (C max ), both in plasma. A human oral PBK model was constructed and calibrated using human volunteer data and adapted to accommodate dermal absorption following human dermal exposure. Use of the MOIE approach based on internal dose metrics predictions provides excellent opportunities to investigate the consequences of variations in human dermal exposure scenarios. It can accommodate within-day variation in plasma concentrations and is scientifically more robust than assuming just an exposure in mg/kg bw/day. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Techniques necessary for multiple tracer quantitative small-animal imaging studies

    International Nuclear Information System (INIS)

    Sharp, Terry L.; Dence, Carmen S.; Engelbach, John A.; Herrero, Pilar; Gropler, Robert J.; Welch, Michael J.

    2005-01-01

    Introduction: An increasing number and variety of studies on rodent models are being conducted using small-animal positron emission tomography scanners. We aimed to determine if animal handling techniques could be developed to perform routine animal imaging in a timely and efficient manner and with minimal effect on animal physiology. These techniques need to be reproducible in the same animal while maintaining hemodynamic and physiological stability. Methods: The necessary techniques include (a) the use of inhalant anesthesia, (b) arterial and venous cannulation for multiple tracer administrations and blood sampling, (c) development of small-volume analytic columns and techniques and (d) measurement of the physiological environment during the imaging session. Results: We provide an example of a cardiac imaging study using four radiotracers ( 15 O-water, 1-[ 11 C]-acetate, 1-[ 11 C]-palmitate and 1-[ 11 C]-glucose) injected into normal rats. Plasma substrates, CO 2 production and total metabolites were measured. The animals remained anesthetized over the entire imaging session, and their physiological state was maintained. Conclusion: The intrastudy stability of the physiological measurements and substrate levels and interstudy reproducibility of the measurements are reported

  10. Toxic phytoplankton in San Francisco Bay

    Science.gov (United States)

    Rodgers, Kristine M.; Garrison, David L.; Cloern, James E.

    1996-01-01

    The Regional Monitoring Program (RMP) was conceived and designed to document the changing distribution and effects of trace substances in San Francisco Bay, with focus on toxic contaminants that have become enriched by human inputs. However, coastal ecosystems like San Francisco Bay also have potential sources of naturally-produced toxic substances that can disrupt food webs and, under extreme circumstances, become threats to public health. The most prevalent source of natural toxins is from blooms of algal species that can synthesize metabolites that are toxic to invertebrates or vertebrates. Although San Francisco Bay is nutrient-rich, it has so far apparently been immune from the epidemic of harmful algal blooms in the world’s nutrient-enriched coastal waters. This absence of acute harmful blooms does not imply that San Francisco Bay has unique features that preclude toxic blooms. No sampling program has been implemented to document the occurrence of toxin-producing algae in San Francisco Bay, so it is difficult to judge the likelihood of such events in the future. This issue is directly relevant to the goals of RMP because harmful species of phytoplankton have the potential to disrupt ecosystem processes that support animal populations, cause severe illness or death in humans, and confound the outcomes of toxicity bioassays such as those included in the RMP. Our purpose here is to utilize existing data on the phytoplankton community of San Francisco Bay to provide a provisional statement about the occurrence, distribution, and potential threats of harmful algae in this Estuary.

  11. Salicylate toxicity model of tinnitus

    Directory of Open Access Journals (Sweden)

    Daniel eStolzberg

    2012-04-01

    Full Text Available Salicylate, the active component of the common drug aspirin, has mild analgesic, antipyretic, and anti-inflammatory effects at moderate doses. At higher doses, however, salicylate temporarily induces moderate hearing loss and the perception of a high-pitch ringing in humans and animals. This phantom perception of sound known as tinnitus is qualitatively similar to the persistent subjective tinnitus induced by high-level noise exposure, ototoxic drugs or aging which affects ~14% of the general population. For over a quarter century, auditory scientists have used the salicylate toxicity model to investigate candidate biochemical and neurophysiological mechanisms underlying phantom sound perception. In this review, we summarize some of the intriguing biochemical and physiological effects associated with salicylate-induced tinnitus, some of which occur in the periphery and others in the central nervous system. The relevance and general utility of the salicylate toxicity model in understanding phantom sound perception in general are discussed.

  12. Development of SCAR marker specific to non-toxic Jatropha curcas L. and designing a novel multiplexing PCR along with nrDNA ITS primers to circumvent the false negative detection

    KAUST Repository

    Mastan, Shaik G.

    2011-05-10

    Jatropha curcas L., a multipurpose shrub, has acquired significant economic importance for its seed oil which can be converted to biodiesel an emerging alternative to petro-diesel. In addition to the commercial value, it is also having medicinal and even high nutritional value to use as animal fodder which is limited due to the toxicity. Development of molecular marker will enable to differentiate non-toxic from toxic variety of J. curcas in a mixed population and also for quality control since the toxic components of J. curcas has deleterious effect on animals. In the present study, the efforts were made to generate the specific SCAR marker for toxic and/or non-toxic J. curcas from RAPD markers. Among the markers specific for toxic and non-toxic varieties, four were selected, purified, cloned, sequenced, and designed primers out of which one set of primers NT-JC/SCAR I/OPQ15-F and R could able to discriminate the non-toxic with toxic Jatropha by giving expected 430 bp size amplification in non-toxic variety. Furthermore, novel multiplex PCR was designed using the nrDNA ITS primers to overcome the false negatives. Present work also demonstrates utility of the conserved regions of nrDNA coding genes in ruling out the artifacts in PCR-like false negatives frequently occur in SCAR due to various reasons. The specific SCAR markers generated in the present investigation will help to distinguish non-toxic from toxic varieties of J. curcas or vice versa, and isolated marker along with designed multiplex protocol has applications in quality control for selective cultivation of non-toxic variety and will also assist in breeding and molecular mapping studies. © 2011 Springer Science+Business Media, LLC.

  13. Role of CYP2E1-mediated metabolism in the acute and vestibular toxicities of nineteen nitriles in the mouse.

    Science.gov (United States)

    Saldaña-Ruíz, Sandra; Soler-Martín, Carla; Llorens, Jordi

    2012-01-25

    Allylnitrile, cis-crotononitrile, and 3,3'-iminodipropionitrile are known to cause vestibular toxicity in rodents, and evidence is available indicating that cis-2-pentenenitrile shares this effect. We evaluated nineteen nitriles for vestibular toxicity in wild type (129S1) and CYP2E1-null mice, including all the above, several neurotoxic nitriles, and structurally similar nitriles. A new acute toxicity test protocol was developed to facilitate evaluation of the vestibular toxicity by a specific behavioral test battery at doses up to sub-lethal levels while using a limited number of animals. A mean number of 8.5±0.3 animals per nitrile, strain and sex was necessary to obtain evidence of vestibular toxicity and optionally an estimation of the lethal dose. For several but not all nitriles, lethal doses significantly increased in CYP2E1-null mice. The protocol revealed the vestibular toxicity of five nitriles, including previously identified ototoxic compounds and one nitrile (trans-crotononitrile) known to have a different profile of neurotoxic effects in the rat. In all five cases, both sexes were affected and no decrease in susceptibility was apparent in CYP2E1-null mice respect to 129S1 mice. Fourteen nitriles caused no vestibular toxicity, including six nitriles tested in CYP2E1-null mice at doses significantly larger than the maximal doses that can be tested in wild type animals. We conclude that only a subset of low molecular weight nitriles is toxic to the vestibular system, that species-dependent differences exist in this vestibular toxicity, and that CYP2E1-mediated metabolism is not involved in this effect of nitriles although it has a role in the acute lethality of some of these compounds. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. Linking waterlogging tolerance with Mn²⁺ toxicity: a case study for barley.

    Science.gov (United States)

    Huang, X; Shabala, S; Shabala, L; Rengel, Z; Wu, X; Zhang, G; Zhou, M

    2015-01-01

    Vast agricultural areas are affected by flooding, causing up to 80% yield reduction and resulting in multibillion dollar losses. Up to now, the focus of plant breeders was predominantly on detrimental effects of anoxia, while other (potentially equally important) traits were essentially neglected; one of these is soil elemental toxicity. Excess water triggers a progressive decrease in soil redox potential, thus increasing the concentration of Mn(2+) that can be toxic to plants if above a specific threshold. This work aimed to quantify the relative contribution of Mn(2+) toxicity to waterlogging stress tolerance, using barley as a case study. Twenty barley (Hordeum vulgare) genotypes contrasting in waterlogging stress tolerance were studied for their ability to cope with toxic (1 mm) amounts of Mn(2+) in the root rhizosphere. Under Mn(2+) toxicity, chlorophyll content of most waterlogging-tolerant genotypes (TX9425, Yerong, CPI-71284-48 and CM72) remained above 60% of the control value, whereas sensitive genotypes (Franklin and Naso Nijo) had 35% less chlorophyll than 35% of controls. Manganese concentration in leaves was not related to visual Mn(2+) toxicity symptoms, suggesting that various Mn(2+) tolerance mechanisms might operate in different tolerant genotypes, i.e. avoidance versus tissue tolerance. The overall significant (r = 0.60) correlation between tolerance to Mn(2+) toxicity and waterlogging in barley suggests that plant breeding for tolerance to waterlogging traits may be advanced by targeting mechanisms conferring tolerance to Mn(2+) toxicity, at least in this species. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

  15. Study on Romanian Consumers’ Opinion Regarding the Animal Welfare Labelling of Animal Products

    Directory of Open Access Journals (Sweden)

    Ludovic Toma Cziszter

    2010-10-01

    Full Text Available The aim of the paper was to investigate the influence some factors on the consumers’ opinion regarding the animal welfare labelling of animal products. The analysed question was: “When purchasing eggs, meat or milk can you easily identify from the label those products sourced from animal welfare friendly production systems?” Respondents chosen only one answer out of the five offered: yes, most of the time; yes, some of the time; no, very rarely; no, never; and don’t know. Thirty three percent of females considered they could find sometime information regarding the animal welfare on the labels, while males considered that this information could be found very rarely. Up to 55 years of age, 50% of the consumers consider that the labels do not contain the information about animal welfare, while after this age most of consumers consider they found this information on the labels. Over 50% of Orthodox and Roman Catholic responders considered that the information on animal welfare on the labels was found some of the time or very rarely. Respondents, irrespective of their living area or monthly income, considered that there is scarce information regarding animal welfare on the labels. Internet access significantly influenced the consumers regarding the availability of the information on the labels.

  16. U.S./Mexico Border environmental study toxics release inventory data, 1988--1992

    Energy Technology Data Exchange (ETDEWEB)

    O`Brien, R.F.; LoPresti, C.A.

    1996-02-01

    This is a report on industrial toxic chemical releases and transfers based on information reported to the Toxics Release Inventory (TRI), a database maintained by the USEPA. This document discusses patterns of toxic chemical releases to the atmosphere, to water, to the land, and to underground injection; and transfers of toxic chemicals to Publicly Owned Treatment Works (POTW), and for disposal, treatment and other off-site transfers during the TRI reporting years 1988--1992. Geographic coverage is limited to the US side of the ``Border Area``, the geographic area situated within 100 km of the US/Mexico international boundary. A primary purpose of this study is to provide background information that can be used in the future development of potential ``indicator variables`` for tracking environmental and public health status in the Border Area in conjunction with the implementation of the North American Free Trade Agreement (NAFTA).

  17. One Health and the Environment: Toxic Cyanobacteria A Case Study

    Science.gov (United States)

    The study of environmental health typically focuses on human populations. However, companion animals, livestock and wildlife also experience adverse health effects from environmental pollutants. Animals may experience direct exposure to pollutants unlike people in most ambient ex...

  18. ADVANCES IN ANIMAL WELFARE FOR FREE-LIVING ANIMALS.

    Science.gov (United States)

    2016-04-01

    Over several decades, animal welfare has grown into its own free-standing field of scientific study, from its early beginnings in laboratory animal research to eventually include exhibited animals and farm animals. While it has always been present to some degree, consideration of animal welfare for free-ranging animals has lagged behind, developing as a field of study in the last 20 yr or so. Part of that increase was that animal welfare legislation was finally applied to studies being done on free-ranging animals. But it is the appreciation by the biologists and veterinarians working on wild animals, in which the quality of their results is largely controlled by the quality of the animals they use in their studies, which has resulted in increased attention to the well-being or welfare of the animals that they use. Other important influences driving the recognition of wildlife welfare have been changes in the public's expectations of how wild animals are dealt with, a shift in focus of wildlife professionals from managing animals that can be hunted or angled to include nongame species, the decrease in participation in hunting and fishing by members of the public, and the entry of large numbers of women into fish and wildlife agencies and departments and into veterinary medicine. Technical improvements have allowed the safe capture and handling of large or dangerous animals as immobilization drugs and equipment have been developed. The increasing use of sedating drugs allows for handling of animals with reduced stress and other impacts. A number of topics, such as toe-clipping, branding, defining which taxa can or cannot feel pain, catch-and-release fishing, and more, remain controversial within wildlife science. How we treat the wild animals that we deal with defines who we are as wildlife professionals, and animal welfare concerns and techniques for free-ranging animals will continue to develop and evolve.

  19. Dioxins and PCBs in game animals: Interspecies comparison and related consumer exposure.

    Science.gov (United States)

    Warenik-Bany, Malgorzata; Strucinski, Pawel; Piskorska-Pliszczynska, Jadwiga

    2016-01-01

    Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (DL-PCB) and non-dioxin-like polychlorinated biphenyls (NDL-PCB) are ubiquitous, persistent toxic compounds that are highly bioaccumulative in nature. Wild-living animals are vulnerable to the negative impacts of human activity. Dioxins and PCBs enter the animal organisms through foraging. Due to the toxicological threat, much attention is paid to these compounds worldwide. The aim of this study was to determine the dioxin contamination status of three game animal species (red deer, roe deer, and wild boar) and compare the PCDD/F and PCB congener bioaccumulation in the muscles, abdominal fat and liver. The chemical analysis was performed by the isotope dilution technique (IDMS) with high-resolution gas chromatography coupled with high-resolution mass spectrometry (HRGC/HRMS). Dioxins and PCBs were found in specimens collected from all studied species, suggesting the presence of the test compounds in the environment of the animals. The highest concentrations were found in the livers of all animals. The toxic equivalent (TEQ) levels in the muscles, adipose tissue and liver were in the order red deer > roe deer > wild boar. PCDD/Fs were the dominant congeners in TEQ value. For all tested species, the dominant contributors to the total WHO-TEQ were PCB-126, 2,3,4,7,8-PeCDF and 1,2,3,7,8-PeCDD. Among the PCDD/F congeners in the deer tissues, OCDD, OCDF and 2,3,4,7,8-PeCDF were dominant, while in wild boar, OCDD, 1,2,3,4,6,7,8-HpCDD and 1,2,3,4,6,7,8-HpCF occurred in the highest amounts. Among PCBs, PCB-105, 118, 156, 138, 153 and 180 were dominant in all species, but with different levels. The regular consumption of muscle meat from game animals should not cause unacceptable dioxin intake above the Tolerable Weekly Intake (TWI) value for children and adults. However, liver consumption should be avoided, especially by children and pregnant or lactating

  20. Studies on the Th biodistribution in internal contamination by the fission track method using animals

    International Nuclear Information System (INIS)

    Ciubotariu, M.; Danis, A.; Dumitrescu, G.; Cucu, M.

    1998-01-01

    In our previous studies on the U internal contamination, qualitative and quantitative results were obtained by using the fission track methods. In order to obtain complete data on the fissionable element internal contamination using animals, we started a similar study using Th as contaminating element and Wistar London breed rats as laboratory animals. Different ways to obtain internal contaminations were investigated: ingestion, inhalation, absorption by skin and through wounds. In this stage, Wistar-London breed rats of the same sex, weight and age were internal contaminated by 1 ml Th solution ingestion for each rat corresponding to an Annual Limit Intake.The animals were kept in normal life conditions and under permanent medical surveillance up to their sacrifice. Also, their evacuations where sampled every 24 hours. They were sacrificed at different time intervals after their contamination: 2 days (RAT 1), 7 days (RAT 2) and 14 days (RAT 3). After sacrifice, their vital organs were sampled, weighed, calcined, reweighed and finally analysed by track detection using the fission track micromapping technique. This technique was used in the following conditions: - mica-muscovite as track detector pre-etched for fossil tracks 18 h in HF; - the neutron irradiations were performed in the nuclear reactor VVR-S Bucharest at the neutron fluences of 3x10 15 - 2x10 16 fast neutrons/cm 2 . In order to check whether there is any U contribution to the fission track densities obtained in track detectors, U existing in the rat body due to food and water, the neutron irradiations of the ensembles were performed with and without 1 mm Cd shielding; - the visualization of the Th induced fission tracks were obtained by chemical etching in HF, 3 h at room temperature; - the Th track micromappings obtained in track detectors were studied by optical microscopy using a stereomicroscope WILD M7S for ensemble study (X6-X31) and a binocular ZEISS JENA microscope for qualitative and